rs10406788

chr19-50286710-G-Achr19-50286710-G-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.4752+16G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.104 in 1,556,746 control chromosomes in the GnomAD database, including 9,926 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1980 hom., cov: 33)
  • Exomes 𝑓: 0.10 (7946 hom.)
• Consequence: MYH14 NM_001145809.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -2.76

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=-0.94).
• BP6: Variant 19-50286710-G-A is Benign according to our data. Variant chr19-50286710-G-A is described in ClinVar as [Benign]. Clinvar id is 257576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-50286710-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.255 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH14	NM_001145809.2	c.4752+16G>A		intron_variant		ENST00000642316.2
MYH14	NM_001077186.2	c.4653+16G>A		intron_variant
MYH14	NM_024729.4	c.4629+16G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH14	ENST00000642316.2	c.4752+16G>A		intron_variant			NM_001145809.2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21072 AN: 152130 Hom.: 1983 Cov.: 33

Gnomad AFR AF: 0.259

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0949

Gnomad ASJ AF: 0.0838

Gnomad EAS AF: 0.0175

Gnomad SAS AF: 0.0558

Gnomad FIN AF: 0.0940

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.101

Gnomad OTH AF: 0.135

GnomAD3 exomes AF: 0.0954 AC: 15402 AN: 161446 Hom.: 1012 AF XY: 0.0937 AC XY: 8089 AN XY: 86340

Gnomad AFR exome AF: 0.275

Gnomad AMR exome AF: 0.0672

Gnomad ASJ exome AF: 0.0946

Gnomad EAS exome AF: 0.0137

Gnomad SAS exome AF: 0.0536

Gnomad FIN exome AF: 0.0995

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.101

GnomAD4 exome AF: 0.101 AC: 141435 AN: 1404498 Hom.: 7946 Cov.: 31 AF XY: 0.0987 AC XY: 68487 AN XY: 693546

Gnomad4 AFR exome AF: 0.262

Gnomad4 AMR exome AF: 0.0698

Gnomad4 ASJ exome AF: 0.0938

Gnomad4 EAS exome AF: 0.0146

Gnomad4 SAS exome AF: 0.0516

Gnomad4 FIN exome AF: 0.0997

Gnomad4 NFE exome AF: 0.103

Gnomad4 OTH exome AF: 0.107

GnomAD4 genome AF: 0.138 AC: 21086 AN: 152248 Hom.: 1980 Cov.: 33 AF XY: 0.135 AC XY: 10047 AN XY: 74446

Gnomad4 AFR AF: 0.259

Gnomad4 AMR AF: 0.0948

Gnomad4 ASJ AF: 0.0838

Gnomad4 EAS AF: 0.0170

Gnomad4 SAS AF: 0.0563

Gnomad4 FIN AF: 0.0940

Gnomad4 NFE AF: 0.101

Gnomad4 OTH AF: 0.133

Alfa AF: 0.109 Hom.: 981

Bravo AF: 0.144

Asia WGS AF: 0.0460 AC: 160 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 16, 2018	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 specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.14
Dann	Benign	0.85

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: rs10406788; hg19: chr19-50789967;