19-50247058-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001145809.2(MYH14):c.1265C>T(p.Ala422Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,461,244 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A422G) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: MYH14 NM_001145809.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.10

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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAdExome at 7 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH14	NM_001145809.2	c.1265C>T	p.Ala422Val	missense_variant	12/43	ENST00000642316.2
MYH14	NM_001077186.2	c.1265C>T	p.Ala422Val	missense_variant	12/42
MYH14	NM_024729.4	c.1241C>T	p.Ala414Val	missense_variant	11/41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH14	ENST00000642316.2	c.1265C>T	p.Ala422Val	missense_variant	12/43		NM_001145809.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000282 AC: 7 AN: 248054 Hom.: 0 AF XY: 0.0000223 AC XY: 3 AN XY: 134674

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000622

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1461244 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 726836

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000126

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

ExAC AF: 0.0000578 AC: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Uncertain	0.083	D
BayesDel_noAF	Uncertain	0.060
Cadd	Pathogenic	26
Dann	Pathogenic	1.0
Eigen	Uncertain	0.28
Eigen_PC	Benign	0.20
FATHMM_MKL	Benign	0.65	D
M_CAP	Uncertain	0.29	D
MetaRNN	Uncertain	0.73	D;D;D;D;D;D;D
MetaSVM	Uncertain	0.67	D
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.74	T
Sift4G	Uncertain	0.0070	D;D;D;.;D;D;D
Polyphen		0.86	P;P;P;P;.;P;P
Vest4		0.57
MutPred		0.72		.;.;Gain of MoRF binding (P = 0.1238);.;.;.;Gain of MoRF binding (P = 0.1238);
MVP		0.94
MPC		0.70
ClinPred		0.47	T
GERP RS		3.7
Varity_R		0.41
gMVP		0.54

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: rs372324948; hg19: chr19-50750315;