dbSNP rs78573213: MYH14:p.Asn1221Asn (chr19-50276186-C-T) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_001145809.2(MYH14):c.3663C>T(p.Asn1221Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00321 in 1,546,934 control chromosomes in the GnomAD database, including 56 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0078 ( 14 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 42 hom. )

Consequence

MYH14
NM_001145809.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -2.91

Publications

1 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 -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.41).

BP6

Variant 19-50276186-C-T is Benign according to our data. Variant chr19-50276186-C-T is described in ClinVar as Benign. ClinVar VariationId is 164185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.91 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00785 (1196/152364) while in subpopulation AFR AF = 0.0218 (907/41590). AF 95% confidence interval is 0.0206. There are 14 homozygotes in GnomAd4. There are 586 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1196 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001145809.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYH14	NM_001145809.2	MANE Select	c.3663C>T	p.Asn1221Asn	synonymous	Exon 28 of 43	NP_001139281.1
MYH14	NM_001077186.2		c.3564C>T	p.Asn1188Asn	synonymous	Exon 27 of 42	NP_001070654.1
MYH14	NM_024729.4		c.3540C>T	p.Asn1180Asn	synonymous	Exon 26 of 41	NP_079005.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
MYH14	ENST00000642316.2	MANE Select	c.3663C>T	p.Asn1221Asn	synonymous	Exon 28 of 43	ENSP00000493594.1
MYH14	ENST00000425460.6	TSL:5	c.3564C>T	p.Asn1188Asn	synonymous	Exon 27 of 42	ENSP00000407879.1
MYH14	ENST00000598205.5	TSL:5	c.3564C>T	p.Asn1188Asn	synonymous	Exon 27 of 42	ENSP00000472543.1

Frequencies

GnomAD3 genomes

AF:

0.00778

AC:

1184

AN:

152246

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0216

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00517

Gnomad ASJ

AF:

0.00374

Gnomad EAS

AF:

0.000578

Gnomad SAS

AF:

0.0120

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.0105

GnomAD2 exomes

AF:

0.00534

AC:

795

AN:

148924

AF XY:

0.00584

show subpopulations

Gnomad AFR exome

AF:

0.0233

Gnomad AMR exome

AF:

0.00490

Gnomad ASJ exome

AF:

0.00317

Gnomad EAS exome

AF:

0.000458

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00167

Gnomad OTH exome

AF:

0.00704

GnomAD4 exome

AF:

0.00270

AC:

3769

AN:

1394570

Hom.:

Cov.:

AF XY:

0.00305

AC XY:

2100

AN XY:

687488

show subpopulations

African (AFR)

AF:

0.0222

AC:

700

AN:

31596

American (AMR)

AF:

0.00539

AC:

192

AN:

35638

Ashkenazi Jewish (ASJ)

AF:

0.00336

AC:

AN:

25012

East Asian (EAS)

AF:

0.000279

AC:

AN:

35876

South Asian (SAS)

AF:

0.0151

AC:

1197

AN:

79092

European-Finnish (FIN)

AF:

0.0000210

AC:

AN:

47588

Middle Eastern (MID)

AF:

0.0162

AC:

AN:

4076

European-Non Finnish (NFE)

AF:

0.00113

AC:

1218

AN:

1077984

Other (OTH)

AF:

0.00522

AC:

301

AN:

57708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

198

396

593

791

989

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

132

198

264

330

<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:

0.00785

AC:

1196

AN:

152364

Hom.:

Cov.:

AF XY:

0.00786

AC XY:

586

AN XY:

74508

show subpopulations

African (AFR)

AF:

0.0218

AC:

907

AN:

41590

American (AMR)

AF:

0.00516

AC:

AN:

15312

Ashkenazi Jewish (ASJ)

AF:

0.00374

AC:

AN:

3472

East Asian (EAS)

AF:

0.000580

AC:

AN:

5176

South Asian (SAS)

AF:

0.0118

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10626

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00159

AC:

108

AN:

68034

Other (OTH)

AF:

0.0104

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

125

187

250

312

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00343

Hom.:

Bravo

AF:

0.00843

Asia WGS

AF:

0.00779

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (3)

not provided (2)

Autosomal dominant nonsyndromic hearing loss 4A (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.41

CADD

Benign

1.8

(source)

DANN

Benign

0.93

PhyloP100

-2.9

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over