rs3745503

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001145809.2(MYH14):c.2827-9A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 1,539,722 control chromosomes in the GnomAD database, including 13,451 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2021 hom., cov: 33)

Exomes 𝑓: 0.12 ( 11430 hom. )

Consequence

MYH14
NM_001145809.2 intron

Scores

Splicing: ADA: 0.00003119

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:10

Conservation

PhyloP100: -2.07

Publications

9 publications found

Variant links:

Genes affected

MYH14 (HGNC:23212): (myosin heavy chain 14) This gene encodes a member of the myosin superfamily. The protein represents a conventional non-muscle myosin; it should not be confused with the unconventional myosin-14 (MYO14). Myosins are actin-dependent motor proteins with diverse functions including regulation of cytokinesis, cell motility, and cell polarity. Mutations in this gene result in one form of autosomal dominant hearing impairment. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

MYH14 Gene-Disease associations (from GenCC):

autosomal dominant nonsyndromic hearing loss 4A
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), Ambry Genetics
peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
nonsyndromic genetic hearing loss
Inheritance: AD Classification: MODERATE Submitted by: ClinGen
autosomal dominant nonsyndromic hearing loss
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

MYH14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 19-50268152-A-C is Benign according to our data. Variant chr19-50268152-A-C is described in ClinVar as Benign. ClinVar VariationId is 44060.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2 link	c.2827-9A>C	intron_variant	Intron 23 of 42	ENST00000642316.2	NP_001139281.1	Q7Z406-2A1L2Z2B3KWH4
MYH14	NM_001077186.2 link	c.2728-9A>C	intron_variant	Intron 22 of 41		NP_001070654.1	Q7Z406-6B3KWH4
MYH14	NM_024729.4 link	c.2704-9A>C	intron_variant	Intron 21 of 40		NP_079005.3	Q7Z406-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2 link	c.2827-9A>C		intron_variant	Intron 23 of 42		NM_001145809.2	ENSP00000493594.1		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22521

AN:

151930

Hom.:

2017

Cov.:

show subpopulations

Gnomad AFR

AF:

0.234

Gnomad AMI

AF:

0.0592

Gnomad AMR

AF:

0.0794

Gnomad ASJ

AF:

0.218

Gnomad EAS

AF:

0.233

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.0794

Gnomad MID

AF:

0.162

Gnomad NFE

AF:

0.107

Gnomad OTH

AF:

0.136

GnomAD2 exomes

AF:

0.140

AC:

20664

AN:

148054

AF XY:

0.146

show subpopulations

Gnomad AFR exome

AF:

0.243

Gnomad AMR exome

AF:

0.0566

Gnomad ASJ exome

AF:

0.214

Gnomad EAS exome

AF:

0.227

Gnomad FIN exome

AF:

0.0858

Gnomad NFE exome

AF:

0.107

Gnomad OTH exome

AF:

0.123

GnomAD4 exome

AF:

0.119

AC:

164582

AN:

1387676

Hom.:

11430

Cov.:

AF XY:

0.122

AC XY:

83231

AN XY:

684026

show subpopulations

African (AFR)

AF:

0.240

AC:

7569

AN:

31494

American (AMR)

AF:

0.0609

AC:

2171

AN:

35660

Ashkenazi Jewish (ASJ)

AF:

0.213

AC:

5346

AN:

25138

East Asian (EAS)

AF:

0.260

AC:

9266

AN:

35644

South Asian (SAS)

AF:

0.229

AC:

18139

AN:

79090

European-Finnish (FIN)

AF:

0.0851

AC:

3581

AN:

42060

Middle Eastern (MID)

AF:

0.152

AC:

663

AN:

4360

European-Non Finnish (NFE)

AF:

0.102

AC:

109978

AN:

1076576

Other (OTH)

AF:

0.136

AC:

7869

AN:

57654

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

7857

15715

23572

31430

39287

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4262

8524

12786

17048

21310

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.148

AC:

22546

AN:

152046

Hom.:

2021

Cov.:

AF XY:

0.148

AC XY:

10968

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.234

AC:

9701

AN:

41456

American (AMR)

AF:

0.0792

AC:

1210

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

758

AN:

3470

East Asian (EAS)

AF:

0.232

AC:

1197

AN:

5162

South Asian (SAS)

AF:

0.239

AC:

1149

AN:

4816

European-Finnish (FIN)

AF:

0.0794

AC:

840

AN:

10584

Middle Eastern (MID)

AF:

0.161

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.107

AC:

7296

AN:

67974

Other (OTH)

AF:

0.139

AC:

294

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

985

1971

2956

3942

4927

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.115

Hom.:

1413

Bravo

AF:

0.149

Asia WGS

AF:

0.241

AC:

836

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 09, 2017

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

2827-9A>C in Intron 23 of MYH14: This variant is not expected to have clinical s ignificance because it has been identified in 18.4% (607/3304) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs3745503). -

Autosomal dominant nonsyndromic hearing loss 4A

Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.24

(source)

DANN

Benign

0.56

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000031

dbscSNV1_RF

Benign

0.012

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over