rs12981413

Variant names:

• chr19-50260632-C-T
• rs12981413
• NM_001145809.2:c.2355-14C>T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001145809.2(MYH14):​c.2355-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.439 in 1,600,692 control chromosomes in the GnomAD database, including 157,937 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (16467 hom., cov: 28)
  • Exomes 𝑓: 0.44 (141470 hom.)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: 0.110

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 19-50260632-C-T is Benign according to our data. Variant chr19-50260632-C-T is described in ClinVar as [Benign]. Clinvar id is 44057.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50260632-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.2355-14C>T		intron_variant	Intron 19 of 42	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.2256-14C>T		intron_variant	Intron 18 of 41		NP_001070654.1
MYH14	NM_024729.4	c.2232-14C>T		intron_variant	Intron 17 of 40		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.2355-14C>T		intron_variant	Intron 19 of 42		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69507 AN: 151346 Hom.: 16445 Cov.: 28

Gnomad AFR AF: 0.467

Gnomad AMI AF: 0.560

Gnomad AMR AF: 0.592

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.392

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.361

Gnomad NFE AF: 0.437

Gnomad OTH AF: 0.440

GnomAD3 exomes AF: 0.454 AC: 111813 AN: 246398 Hom.: 26624 AF XY: 0.442 AC XY: 59172 AN XY: 133854

Gnomad AFR exome AF: 0.468

Gnomad AMR exome AF: 0.662

Gnomad ASJ exome AF: 0.283

Gnomad EAS exome AF: 0.302

Gnomad SAS exome AF: 0.385

Gnomad FIN exome AF: 0.526

Gnomad NFE exome AF: 0.433

Gnomad OTH exome AF: 0.443

GnomAD4 exome AF: 0.437 AC: 633783 AN: 1449228 Hom.: 141470 Cov.: 31 AF XY: 0.434 AC XY: 313544 AN XY: 721636

Gnomad4 AFR exome AF: 0.467

Gnomad4 AMR exome AF: 0.649

Gnomad4 ASJ exome AF: 0.292

Gnomad4 EAS exome AF: 0.322

Gnomad4 SAS exome AF: 0.388

Gnomad4 FIN exome AF: 0.520

Gnomad4 NFE exome AF: 0.436

Gnomad4 OTH exome AF: 0.426

GnomAD4 genome AF: 0.459 AC: 69577 AN: 151464 Hom.: 16467 Cov.: 28 AF XY: 0.465 AC XY: 34387 AN XY: 73974

Gnomad4 AFR AF: 0.467

Gnomad4 AMR AF: 0.592

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.311

Gnomad4 SAS AF: 0.393

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.437

Gnomad4 OTH AF: 0.435

Alfa AF: 0.426 Hom.: 2623

Bravo AF: 0.465

Asia WGS AF: 0.403 AC: 1398 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 22, 2018

GeneDx

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

- -

not specified Benign:2

May 07, 2012

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

2355-14C>T in Intron 19 of MYH14: This variant is not expected to have clinical significance because it has been identified in 45.9% (1652/3600) of African Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs12981413). -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Autosomal dominant nonsyndromic hearing loss 4A Benign:2

Jan 12, 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. -

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	-0.88
CADD	Benign	5.6
DANN	Benign	0.64

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

LitVar

Other links and lift over

dbSNP: rs12981413; hg19: chr19-50763889; COSMIC: COSV51812511; COSMIC: COSV51812511;