rs73061136

Variant names:

• chr19-50249640-G-A
• rs73061136
• NM_001145809.2:c.1483-10G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145809.2(MYH14):​c.1483-10G>A variant causes a 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 intron
• Scores: Splicing: ADA: 0.0003115
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.44
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -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.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.1483-10G>A		intron_variant	Intron 13 of 42	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.1483-10G>A		intron_variant	Intron 13 of 41		NP_001070654.1
MYH14	NM_024729.4	c.1459-10G>A		intron_variant	Intron 12 of 40		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.1483-10G>A		intron_variant	Intron 13 of 42		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes AF: 0.0893 AC: 11000 AN: 123184 Hom.: 520 Cov.: 32

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

GnomAD2 exomes AF: 0.0843 AC: 21175 AN: 251316 AF XY: 0.0780

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 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.: 36 AF XY: 0.0660 AC XY: 47037 AN XY: 712394

African (AFR) AF: 0.0693 AC: 2270 AN: 32772

American (AMR) AF: 0.207 AC: 9085 AN: 43808

Ashkenazi Jewish (ASJ) AF: 0.0816 AC: 2048 AN: 25084

East Asian (EAS) AF: 0.000323 AC: 12 AN: 37172

South Asian (SAS) AF: 0.0427 AC: 3638 AN: 85182

European-Finnish (FIN) AF: 0.154 AC: 7955 AN: 51754

Middle Eastern (MID) AF: 0.0665 AC: 357 AN: 5366

European-Non Finnish (NFE) AF: 0.0612 AC: 66872 AN: 1093048

Other (OTH) AF: 0.0695 AC: 4072 AN: 58612

GnomAD4 genome AF: 0.0895 AC: 11030 AN: 123286 Hom.: 527 Cov.: 32 AF XY: 0.0927 AC XY: 5554 AN XY: 59918

African (AFR) AF: 0.0830 AC: 2802 AN: 33746

American (AMR) AF: 0.162 AC: 1949 AN: 12016

Ashkenazi Jewish (ASJ) AF: 0.0927 AC: 268 AN: 2892

East Asian (EAS) AF: 0.00247 AC: 10 AN: 4054

South Asian (SAS) AF: 0.0487 AC: 179 AN: 3672

European-Finnish (FIN) AF: 0.184 AC: 1503 AN: 8168

Middle Eastern (MID) AF: 0.104 AC: 23 AN: 222

European-Non Finnish (NFE) AF: 0.0731 AC: 4097 AN: 56034

Other (OTH) AF: 0.106 AC: 180 AN: 1700

Alfa AF: 0.0665 Hom.: 95

Bravo AF: 0.0749

Asia WGS AF: 0.0350 AC: 121 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 30, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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). -

Aug 25, 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. -

not provided Benign:2

Feb 03, 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

- -

Autosomal dominant nonsyndromic hearing loss 4A Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.7
DANN	Benign	0.72
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs73061136; hg19: chr19-50752897; COSMIC: COSV51815766; COSMIC: COSV51815766;