19-50280037-G-T

Variant names:

• chr19-50280037-G-T
• rs148054042
• NM_001145809.2:c.4033G>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001145809.2(MYH14):​c.4033G>T​(p.Ala1345Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 18/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MYH14 NM_001145809.2 missense, splice_region
• Scores: Splicing: ADA: 0.06561
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.545

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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.053585947).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.4033G>T	p.Ala1345Ser	missense_variant, splice_region_variant	Exon 31 of 43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.3934G>T	p.Ala1312Ser	missense_variant, splice_region_variant	Exon 30 of 42		NP_001070654.1
MYH14	NM_024729.4	c.3910G>T	p.Ala1304Ser	missense_variant, splice_region_variant	Exon 29 of 41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.4033G>T	p.Ala1345Ser	missense_variant, splice_region_variant	Exon 31 of 43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Benign	0.31
DEOGEN2	Benign	0.11	.;.;T;.;.;T;T
Eigen	Benign	-0.65
Eigen_PC	Benign	-0.56
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.66	.;T;T;.;T;.;T
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.054	T;T;T;T;T;T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	0.55	.;.;N;.;.;N;.
PrimateAI	Benign	0.38	T
PROVEAN	Benign	-0.080	.;N;.;.;.;.;.
REVEL	Benign	0.048
Sift	Benign	0.90	.;T;.;.;.;.;.
Sift4G	Benign	0.94	T;T;T;.;T;T;T
Polyphen		0.0020	B;B;B;B;B;B;.
Vest4		0.21
MutPred		0.34		.;.;Gain of phosphorylation at A1304 (P = 0.0066);.;.;Gain of phosphorylation at A1304 (P = 0.0066);.;
MVP		0.55
MPC		0.14
ClinPred		0.032	T
GERP RS		2.2
Varity_R		0.034
gMVP		0.094

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.066
dbscSNV1_RF	Benign	0.51
SpliceAI score (max)		0.010		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: rs148054042; hg19: chr19-50783294;