chr19-50293703-C-T

Variant names:

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.5469+16C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.737 in 1,542,138 control chromosomes in the GnomAD database, including 424,673 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.66 ( 35484 hom., cov: 33)

Exomes 𝑓: 0.74 ( 389189 hom. )

Consequence

MYH14
NM_001145809.2 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: -4.41

Publications

10 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=-0.86).

BP6

Variant 19-50293703-C-T is Benign according to our data. Variant chr19-50293703-C-T is described in ClinVar as Benign. ClinVar VariationId is 257578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.901 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2 link	c.5469+16C>T	intron_variant	Intron 39 of 42	ENST00000642316.2	NP_001139281.1	Q7Z406-2A1L2Z2B3KWH4
MYH14	NM_001077186.2 link	c.5370+16C>T	intron_variant	Intron 38 of 41		NP_001070654.1	Q7Z406-6B3KWH4
MYH14	NM_024729.4 link	c.5346+16C>T	intron_variant	Intron 37 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.5469+16C>T		intron_variant	Intron 39 of 42		NM_001145809.2	ENSP00000493594.1		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.661

AC:

100501

AN:

152014

Hom.:

35464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.394

Gnomad AMI

AF:

0.646

Gnomad AMR

AF:

0.773

Gnomad ASJ

AF:

0.722

Gnomad EAS

AF:

0.922

Gnomad SAS

AF:

0.779

Gnomad FIN

AF:

0.764

Gnomad MID

AF:

0.722

Gnomad NFE

AF:

0.750

Gnomad OTH

AF:

0.685

GnomAD2 exomes

AF:

0.754

AC:

149415

AN:

198216

AF XY:

0.757

show subpopulations

Gnomad AFR exome

AF:

0.388

Gnomad AMR exome

AF:

0.857

Gnomad ASJ exome

AF:

0.711

Gnomad EAS exome

AF:

0.931

Gnomad FIN exome

AF:

0.768

Gnomad NFE exome

AF:

0.747

Gnomad OTH exome

AF:

0.747

GnomAD4 exome

AF:

0.745

AC:

1035465

AN:

1390006

Hom.:

389189

Cov.:

AF XY:

0.746

AC XY:

509743

AN XY:

683016

show subpopulations

African (AFR)

AF:

0.384

AC:

12159

AN:

31626

American (AMR)

AF:

0.846

AC:

29639

AN:

35030

Ashkenazi Jewish (ASJ)

AF:

0.713

AC:

15314

AN:

21474

East Asian (EAS)

AF:

0.910

AC:

35425

AN:

38948

South Asian (SAS)

AF:

0.785

AC:

58582

AN:

74664

European-Finnish (FIN)

AF:

0.766

AC:

38954

AN:

50878

Middle Eastern (MID)

AF:

0.731

AC:

3909

AN:

5348

European-Non Finnish (NFE)

AF:

0.744

AC:

799947

AN:

1074786

Other (OTH)

AF:

0.725

AC:

41536

AN:

57252

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

12546

25092

37637

50183

62729

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20046

40092

60138

80184

100230

<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:

0.661

AC:

100560

AN:

152132

Hom.:

35484

Cov.:

AF XY:

0.669

AC XY:

49765

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.394

AC:

16345

AN:

41468

American (AMR)

AF:

0.774

AC:

11827

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.722

AC:

2507

AN:

3472

East Asian (EAS)

AF:

0.923

AC:

4782

AN:

5182

South Asian (SAS)

AF:

0.779

AC:

3760

AN:

4824

European-Finnish (FIN)

AF:

0.764

AC:

8085

AN:

10584

Middle Eastern (MID)

AF:

0.718

AC:

211

AN:

294

European-Non Finnish (NFE)

AF:

0.750

AC:

51004

AN:

68000

Other (OTH)

AF:

0.688

AC:

1451

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1572

3145

4717

6290

7862

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

790

1580

2370

3160

3950

<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:

0.722

Hom.:

19153

Bravo

AF:

0.651

Asia WGS

AF:

0.838

AC:

2912

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 22, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 4A

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

-0.86

CADD

Benign

0.034

(source)

DANN

Benign

0.52

PhyloP100

-4.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

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