19-50268179-C-G

Position:

• chr19-50268179-C-G

Variant summary

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

The NM_001145809.2(MYH14):​c.2845C>G​(p.Arg949Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,396,498 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: 33)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: MYH14 NM_001145809.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.793

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=0.20479834).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.2845C>G	p.Arg949Gly	missense_variant	24/43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.2746C>G	p.Arg916Gly	missense_variant	23/42		NP_001070654.1
MYH14	NM_024729.4	c.2722C>G	p.Arg908Gly	missense_variant	22/41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.2845C>G	p.Arg949Gly	missense_variant	24/43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000647 AC: 1 AN: 154448 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 82120

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: 0.0000162

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1396498 Hom.: 0 Cov.: 34 AF XY: 0.00000290 AC XY: 2 AN XY: 689000

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: 0.00000185

Gnomad4 OTH exome AF: 0.0000173

GnomAD4 genome Cov.: 33

Bravo AF: 0.0000189

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.010	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	21
DANN	Benign	0.96
DEOGEN2	Benign	0.31	.;.;T;.;T;.;T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.041
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Uncertain	0.91	.;D;D;.;D;D;.
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.20	T;T;T;T;T;T;T
MetaSVM	Benign	-0.68	T
MutationAssessor	Benign	1.1	.;.;L;.;.;.;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.3	.;N;.;.;.;.;.
REVEL	Uncertain	0.35
Sift	Benign	0.38	.;T;.;.;.;.;.
Sift4G	Benign	0.38	T;T;T;.;T;T;T
Polyphen		0.14	B;B;B;P;.;P;B
Vest4		0.35
MutPred		0.42		.;.;Loss of stability (P = 0.0343);.;.;.;Loss of stability (P = 0.0343);
MVP		0.85
MPC		0.79
ClinPred		0.21	T
GERP RS		3.9
Varity_R		0.21
gMVP		0.30

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: rs755994602; hg19: chr19-50771436;