19-50210385-C-T

Position:

• chr19-50210385-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001145809.2(MYH14):​c.20C>T​(p.Ser7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000139 in 1,434,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYH14 NM_001145809.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.76

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17922744).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.20C>T	p.Ser7Leu	missense_variant	2/43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.20C>T	p.Ser7Leu	missense_variant	2/42		NP_001070654.1
MYH14	NM_024729.4	c.20C>T	p.Ser7Leu	missense_variant	2/41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.20C>T	p.Ser7Leu	missense_variant	2/43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000139 AC: 2 AN: 1434156 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 712224

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: 0.0000121

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.09e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Uncertain	0.017	T
BayesDel_noAF	Benign	-0.21
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	.;.;T;.;T;.;.;T
Eigen	Benign	-0.36
Eigen_PC	Benign	-0.33
FATHMM_MKL	Benign	0.21	N
LIST_S2	Uncertain	0.88	.;D;D;.;D;D;D;.
M_CAP	Benign	0.037	D
MetaRNN	Benign	0.18	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.8	L;L;L;L;.;L;.;L
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-0.81	.;N;N;.;.;.;.;.
REVEL	Benign	0.22
Sift	Pathogenic	0.0	.;D;D;.;.;.;.;.
Sift4G	Pathogenic	0.0	D;D;D;.;T;D;.;D
Polyphen		0.52	P;P;B;P;.;P;.;B
Vest4		0.28
MutPred		0.26		Loss of glycosylation at S7 (P = 0.0127);Loss of glycosylation at S7 (P = 0.0127);Loss of glycosylation at S7 (P = 0.0127);Loss of glycosylation at S7 (P = 0.0127);Loss of glycosylation at S7 (P = 0.0127);Loss of glycosylation at S7 (P = 0.0127);Loss of glycosylation at S7 (P = 0.0127);Loss of glycosylation at S7 (P = 0.0127);
MVP		0.35
MPC		0.48
ClinPred		0.59	D
GERP RS		3.9
Varity_R		0.12
gMVP		0.39

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: rs119103279; hg19: chr19-50713642;