dbSNP rs77895476: MYH14:p.Val630Val (chr19-50252698-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001145809.2(MYH14):c.1890C>T(p.Val630Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0166 in 1,601,110 control chromosomes in the GnomAD database, including 487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.032 ( 136 hom., cov: 32)

Exomes 𝑓: 0.015 ( 351 hom. )

Consequence

MYH14
NM_001145809.2 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -4.40

Publications

7 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: Ambry Genetics, Labcorp Genetics (formerly Invitae)
peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Orphanet, 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

new If you want to explore the variant's impact on the transcript NM_001145809.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67).

BP6

Variant 19-50252698-C-T is Benign according to our data. Variant chr19-50252698-C-T is described in ClinVar as Benign. ClinVar VariationId is 44051.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.4 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.089 is higher than 0.05.

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	UniProt
MYH14	NM_001145809.2	MANE Select	c.1890C>T	p.Val630Val	synonymous	Exon 16 of 43	NP_001139281.1	Q7Z406-2
MYH14	NM_001077186.2		c.1890C>T	p.Val630Val	synonymous	Exon 16 of 42	NP_001070654.1	Q7Z406-6
MYH14	NM_024729.4		c.1866C>T	p.Val622Val	synonymous	Exon 15 of 41	NP_079005.3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MYH14	ENST00000642316.2	MANE Select	c.1890C>T	p.Val630Val	synonymous	Exon 16 of 43	ENSP00000493594.1	Q7Z406-2
MYH14	ENST00000599920.5	TSL:1	c.1890C>T	p.Val630Val	synonymous	Exon 16 of 24	ENSP00000469573.1	M0QY43
MYH14	ENST00000425460.6	TSL:5	c.1890C>T	p.Val630Val	synonymous	Exon 16 of 42	ENSP00000407879.1	Q7Z406-6

Frequencies

GnomAD3 genomes

AF:

0.0322

AC:

4905

AN:

152152

Hom.:

136

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0715

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.0227

Gnomad ASJ

AF:

0.0245

Gnomad EAS

AF:

0.0963

Gnomad SAS

AF:

0.0112

Gnomad FIN

AF:

0.0186

Gnomad MID

AF:

0.0159

Gnomad NFE

AF:

0.0101

Gnomad OTH

AF:

0.0301

GnomAD2 exomes

AF:

0.0229

AC:

5232

AN:

228332

AF XY:

0.0213

show subpopulations

Gnomad AFR exome

AF:

0.0750

Gnomad AMR exome

AF:

0.0126

Gnomad ASJ exome

AF:

0.0209

Gnomad EAS exome

AF:

0.0982

Gnomad FIN exome

AF:

0.0173

Gnomad NFE exome

AF:

0.0120

Gnomad OTH exome

AF:

0.0208

GnomAD4 exome

AF:

0.0150

AC:

21676

AN:

1448840

Hom.:

351

Cov.:

AF XY:

0.0145

AC XY:

10428

AN XY:

719462

show subpopulations

African (AFR)

AF:

0.0758

AC:

2514

AN:

33148

American (AMR)

AF:

0.0132

AC:

566

AN:

42876

Ashkenazi Jewish (ASJ)

AF:

0.0203

AC:

526

AN:

25860

East Asian (EAS)

AF:

0.0810

AC:

3159

AN:

39024

South Asian (SAS)

AF:

0.0101

AC:

847

AN:

83808

European-Finnish (FIN)

AF:

0.0160

AC:

835

AN:

52324

Middle Eastern (MID)

AF:

0.0234

AC:

135

AN:

5762

European-Non Finnish (NFE)

AF:

0.0106

AC:

11766

AN:

1106124

Other (OTH)

AF:

0.0222

AC:

1328

AN:

59914

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

Heterozygous variant carriers

1063

2126

3189

4252

5315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

544

1088

1632

2176

2720

<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:

0.0322

AC:

4907

AN:

152270

Hom.:

136

Cov.:

AF XY:

0.0323

AC XY:

2406

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0714

AC:

2965

AN:

41548

American (AMR)

AF:

0.0226

AC:

346

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0245

AC:

AN:

3472

East Asian (EAS)

AF:

0.0959

AC:

497

AN:

5180

South Asian (SAS)

AF:

0.0116

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0186

AC:

197

AN:

10612

Middle Eastern (MID)

AF:

0.0137

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0101

AC:

686

AN:

68028

Other (OTH)

AF:

0.0307

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

228

457

685

914

1142

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

112

168

224

280

<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:

0.0279

Hom.:

Bravo

AF:

0.0357

Asia WGS

AF:

0.0490

AC:

172

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (3)

Autosomal dominant nonsyndromic hearing loss 4A (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

0.19

(source)

DANN

Benign

0.93

PhyloP100

-4.4

Mutation Taster

=99/1

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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