rs76579307

chr19-50276212-C-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.3680+9C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,525,978 control chromosomes in the GnomAD database, including 39,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3347 hom., cov: 33)
  • Exomes 𝑓: 0.22 (35957 hom.)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -3.50

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=-0.89).
• BP6: Variant 19-50276212-C-T is Benign according to our data. Variant chr19-50276212-C-T is described in ClinVar as [Benign]. Clinvar id is 44067.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50276212-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.236 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH14	NM_001145809.2	c.3680+9C>T		intron_variant		ENST00000642316.2
MYH14	NM_001077186.2	c.3581+9C>T		intron_variant
MYH14	NM_024729.4	c.3557+9C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH14	ENST00000642316.2	c.3680+9C>T		intron_variant			NM_001145809.2

Frequencies

GnomAD3 genomes AF: 0.201 AC: 30533 AN: 152090 Hom.: 3347 Cov.: 33

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.391

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.0322

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.301

Gnomad MID AF: 0.136

Gnomad NFE AF: 0.239

Gnomad OTH AF: 0.195

GnomAD3 exomes AF: 0.184 AC: 24583 AN: 133464 Hom.: 2638 AF XY: 0.182 AC XY: 13109 AN XY: 71856

Gnomad AFR exome AF: 0.157

Gnomad AMR exome AF: 0.149

Gnomad ASJ exome AF: 0.161

Gnomad EAS exome AF: 0.0199

Gnomad SAS exome AF: 0.123

Gnomad FIN exome AF: 0.301

Gnomad NFE exome AF: 0.239

Gnomad OTH exome AF: 0.198

GnomAD4 exome AF: 0.222 AC: 305190 AN: 1373770 Hom.: 35957 Cov.: 30 AF XY: 0.219 AC XY: 148194 AN XY: 675730

Gnomad4 AFR exome AF: 0.152

Gnomad4 AMR exome AF: 0.146

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.0177

Gnomad4 SAS exome AF: 0.121

Gnomad4 FIN exome AF: 0.291

Gnomad4 NFE exome AF: 0.241

Gnomad4 OTH exome AF: 0.197

GnomAD4 genome AF: 0.201 AC: 30539 AN: 152208 Hom.: 3347 Cov.: 33 AF XY: 0.201 AC XY: 14966 AN XY: 74420

Gnomad4 AFR AF: 0.156

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.0323

Gnomad4 SAS AF: 0.115

Gnomad4 FIN AF: 0.301

Gnomad4 NFE AF: 0.240

Gnomad4 OTH AF: 0.193

Alfa AF: 0.216 Hom.: 813

Bravo AF: 0.190

Asia WGS AF: 0.0960 AC: 333 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:6

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Apr 30, 2012	3680+9C>T in Intron 28 of MYH14: This variant is not expected to have clinical s ignificance because it is not located within the conserved splice consensus sequ ence and has been identified in 21.5% (1419/6596) of European American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS; dbSNP rs76579307). -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 03, 2016	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 09, 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. -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -

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	-0.89
Cadd	Benign	0.23
Dann	Benign	0.75

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: rs76579307; hg19: chr19-50779469;