rs73061136

Positions:

chr19-50249640-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001145809.2(MYH14):c.1483-10G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.069 in 1,556,084 control chromosomes in the GnomAD database, including 4,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.089 ( 527 hom., cov: 32)

Exomes 𝑓: 0.067 ( 4077 hom. )

Consequence

MYH14
NM_001145809.2 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0003115

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.44

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 19-50249640-G-A is Benign according to our data. Variant chr19-50249640-G-A is described in ClinVar as [Benign]. Clinvar id is 44049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50249640-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE
MYH14	NM_001145809.2 linkuse as main transcript	c.1483-10G>A	splice_polypyrimidine_tract_variant, intron_variant	ENST00000642316.2
MYH14	NM_001077186.2 linkuse as main transcript	c.1483-10G>A	splice_polypyrimidine_tract_variant, intron_variant
MYH14	NM_024729.4 linkuse as main transcript	c.1459-10G>A	splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH14	ENST00000642316.2 linkuse as main transcript	c.1483-10G>A		splice_polypyrimidine_tract_variant, intron_variant			NM_001145809.2		Q7Z406-2

Frequencies

GnomAD3 genomes

AF:

0.0893

AC:

11000

AN:

123184

Hom.:

520

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0827

Gnomad AMI

AF:

0.0243

Gnomad AMR

AF:

0.162

Gnomad ASJ

AF:

0.0927

Gnomad EAS

AF:

0.00221

Gnomad SAS

AF:

0.0489

Gnomad FIN

AF:

0.184

Gnomad MID

AF:

0.0958

Gnomad NFE

AF:

0.0731

Gnomad OTH

AF:

0.107

GnomAD3 exomes

AF:

0.0843

AC:

21175

AN:

251316

Hom.:

1441

AF XY:

0.0780

AC XY:

10595

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.0699

Gnomad AMR exome

AF:

0.213

Gnomad ASJ exome

AF:

0.0760

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0405

Gnomad FIN exome

AF:

0.145

Gnomad NFE exome

AF:

0.0617

Gnomad OTH exome

AF:

0.0850

GnomAD4 exome

AF:

0.0672

AC:

96309

AN:

1432798

Hom.:

4077

Cov.:

AF XY:

0.0660

AC XY:

47037

AN XY:

712394

show subpopulations

Gnomad4 AFR exome

AF:

0.0693

Gnomad4 AMR exome

AF:

0.207

Gnomad4 ASJ exome

AF:

0.0816

Gnomad4 EAS exome

AF:

0.000323

Gnomad4 SAS exome

AF:

0.0427

Gnomad4 FIN exome

AF:

0.154

Gnomad4 NFE exome

AF:

0.0612

Gnomad4 OTH exome

AF:

0.0695

GnomAD4 genome

AF:

0.0895

AC:

11030

AN:

123286

Hom.:

527

Cov.:

AF XY:

0.0927

AC XY:

5554

AN XY:

59918

show subpopulations

Gnomad4 AFR

AF:

0.0830

Gnomad4 AMR

AF:

0.162

Gnomad4 ASJ

AF:

0.0927

Gnomad4 EAS

AF:

0.00247

Gnomad4 SAS

AF:

0.0487

Gnomad4 FIN

AF:

0.184

Gnomad4 NFE

AF:

0.0731

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.0665

Hom.:

Bravo

AF:

0.0749

Asia WGS

AF:

0.0350

AC:

121

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	1483-10G>A in Intron 13 of MYH14: This variant is not expected to have clinical significance because it has been identified in 7.3% (272/3738) of African Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs73061136). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 25, 2017	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. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Autosomal dominant nonsyndromic hearing loss 4A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

4.7

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00031

dbscSNV1_RF

Benign

0.0

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over