19-50268378-T-C

Position:

• chr19-50268378-T-C

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.3033+11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.874 in 1,555,034 control chromosomes in the GnomAD database, including 594,557 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.87 (57768 hom., cov: 33)
  • Exomes 𝑓: 0.87 (536789 hom.)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.209

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=-0.9).
• BP6: Variant 19-50268378-T-C is Benign according to our data. Variant chr19-50268378-T-C is described in ClinVar as [Benign]. Clinvar id is 44063.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50268378-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.3033+11T>C		intron_variant		ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.2934+11T>C		intron_variant			NP_001070654.1
MYH14	NM_024729.4	c.2910+11T>C		intron_variant			NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.3033+11T>C		intron_variant			NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes AF: 0.871 AC: 132493 AN: 152154 Hom.: 57727 Cov.: 33

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.838

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.868

Gnomad EAS AF: 0.857

Gnomad SAS AF: 0.886

Gnomad FIN AF: 0.907

Gnomad MID AF: 0.858

Gnomad NFE AF: 0.871

Gnomad OTH AF: 0.853

GnomAD3 exomes AF: 0.879 AC: 141371 AN: 160754 Hom.: 62162 AF XY: 0.878 AC XY: 75118 AN XY: 85572

Gnomad AFR exome AF: 0.858

Gnomad AMR exome AF: 0.913

Gnomad ASJ exome AF: 0.857

Gnomad EAS exome AF: 0.849

Gnomad SAS exome AF: 0.886

Gnomad FIN exome AF: 0.902

Gnomad NFE exome AF: 0.871

Gnomad OTH exome AF: 0.874

GnomAD4 exome AF: 0.875 AC: 1227108 AN: 1402762 Hom.: 536789 Cov.: 48 AF XY: 0.875 AC XY: 605809 AN XY: 692456

Gnomad4 AFR exome AF: 0.852

Gnomad4 AMR exome AF: 0.907

Gnomad4 ASJ exome AF: 0.859

Gnomad4 EAS exome AF: 0.876

Gnomad4 SAS exome AF: 0.885

Gnomad4 FIN exome AF: 0.901

Gnomad4 NFE exome AF: 0.873

Gnomad4 OTH exome AF: 0.873

GnomAD4 genome AF: 0.871 AC: 132587 AN: 152272 Hom.: 57768 Cov.: 33 AF XY: 0.872 AC XY: 64952 AN XY: 74458

Gnomad4 AFR AF: 0.857

Gnomad4 AMR AF: 0.884

Gnomad4 ASJ AF: 0.868

Gnomad4 EAS AF: 0.857

Gnomad4 SAS AF: 0.886

Gnomad4 FIN AF: 0.907

Gnomad4 NFE AF: 0.871

Gnomad4 OTH AF: 0.853

Alfa AF: 0.870 Hom.: 84900

Bravo AF: 0.870

Asia WGS AF: 0.880 AC: 3060 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:10

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:4

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
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	May 07, 2012	3033+11T>C in Intron 24 of MYH14: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence and has been identified in 13.5% (468/3466) of African American chromosome s from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.w ashington.edu/EVS; dbSNP rs930086). -

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 22, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

Autosomal dominant nonsyndromic hearing loss 4A Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Sep 05, 2021	- -

Peripheral neuropathy-myopathy-hoarseness-hearing loss syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Sep 05, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.8
DANN	Benign	0.60

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: rs930086; hg19: chr19-50771635; COSMIC: COSV104386293;