rs78573213

chr19-50276186-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BS1 BS2

The NM_001145809.2(MYH14):c.3663C>T(p.Asn1221=) 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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.91

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 -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 id is 164185.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50276186-C-T is described in Lovd as [Benign].
• 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 male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 1184 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH14	NM_001145809.2	c.3663C>T	p.Asn1221=	synonymous_variant	28/43	ENST00000642316.2
MYH14	NM_001077186.2	c.3564C>T	p.Asn1188=	synonymous_variant	27/42
MYH14	NM_024729.4	c.3540C>T	p.Asn1180=	synonymous_variant	26/41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH14	ENST00000642316.2	c.3663C>T	p.Asn1221=	synonymous_variant	28/43		NM_001145809.2

Frequencies

GnomAD3 genomes AF: 0.00778 AC: 1184 AN: 152246 Hom.: 10 Cov.: 33

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

GnomAD3 exomes AF: 0.00534 AC: 795 AN: 148924 Hom.: 8 AF XY: 0.00584 AC XY: 467 AN XY: 79960

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 SAS exome AF: 0.0152

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.: 42 Cov.: 32 AF XY: 0.00305 AC XY: 2100 AN XY: 687488

Gnomad4 AFR exome AF: 0.0222

Gnomad4 AMR exome AF: 0.00539

Gnomad4 ASJ exome AF: 0.00336

Gnomad4 EAS exome AF: 0.000279

Gnomad4 SAS exome AF: 0.0151

Gnomad4 FIN exome AF: 0.0000210

Gnomad4 NFE exome AF: 0.00113

Gnomad4 OTH exome AF: 0.00522

GnomAD4 genome AF: 0.00785 AC: 1196 AN: 152364 Hom.: 14 Cov.: 33 AF XY: 0.00786 AC XY: 586 AN XY: 74508

Gnomad4 AFR AF: 0.0218

Gnomad4 AMR AF: 0.00516

Gnomad4 ASJ AF: 0.00374

Gnomad4 EAS AF: 0.000580

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00159

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00343 Hom.: 2

Bravo AF: 0.00843

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Feb 26, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	May 07, 2012	Asn1221Asn in Exon 28 of MYH14: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 1.7% (61/3586) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs78573213). -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Dec 27, 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. -

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. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.41
Cadd	Benign	1.8
Dann	Benign	0.93

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: rs78573213; hg19: chr19-50779443;