rs201746408

Positions:

• chr19-50271473-C-A
• chr19-50271473-C-T

Variant summary

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

The NM_001145809.2(MYH14):​c.3098C>A​(p.Thr1033Lys) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,455,816 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MYH14 NM_001145809.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.64

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.3098C>A	p.Thr1033Lys	missense_variant	25/43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.2999C>A	p.Thr1000Lys	missense_variant	24/42		NP_001070654.1
MYH14	NM_024729.4	c.2975C>A	p.Thr992Lys	missense_variant	23/41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.3098C>A	p.Thr1033Lys	missense_variant	25/43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1455816 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 723508

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: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.60
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Benign	0.97
DEOGEN2	Uncertain	0.51	.;.;D;.;T;.;D
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.32
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.84	.;T;T;.;D;T;.
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.46	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.0028	T
MutationAssessor	Uncertain	2.1	.;.;M;.;.;.;M
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-3.1	.;D;.;.;.;.;.
REVEL	Uncertain	0.31
Sift	Uncertain	0.029	.;D;.;.;.;.;.
Sift4G	Uncertain	0.015	D;D;D;.;T;D;D
Polyphen		0.94	P;P;P;D;.;D;P
Vest4		0.57
MutPred		0.36		.;.;Gain of MoRF binding (P = 0.0289);.;.;.;Gain of MoRF binding (P = 0.0289);
MVP		0.58
MPC		0.63
ClinPred		0.92	D
GERP RS		3.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.11
gMVP		0.45

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs201746408; hg19: chr19-50774730; COSMIC: COSV51826998;