rs727503226

Positions:

• chr19-50280357-C-A
• chr19-50280357-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001145809.2(MYH14):​c.4264C>A​(p.Arg1422Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MYH14 NM_001145809.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.28

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.36559346).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYH14	NM_001145809.2	c.4264C>A	p.Arg1422Ser	missense_variant	32/43	ENST00000642316.2	NP_001139281.1
MYH14	NM_001077186.2	c.4165C>A	p.Arg1389Ser	missense_variant	31/42		NP_001070654.1
MYH14	NM_024729.4	c.4141C>A	p.Arg1381Ser	missense_variant	30/41		NP_079005.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYH14	ENST00000642316.2	c.4264C>A	p.Arg1422Ser	missense_variant	32/43		NM_001145809.2	ENSP00000493594.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1393562 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 686678

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: 0.00

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	Uncertain	0.41
BayesDel_addAF	Uncertain	0.034	T
BayesDel_noAF	Benign	-0.19
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.53	.;.;.;D;.;.;D;T
Eigen	Benign	-0.048
Eigen_PC	Benign	-0.24
FATHMM_MKL	Benign	0.26	N
LIST_S2	Benign	0.83	.;T;T;T;.;T;.;T
M_CAP	Uncertain	0.15	D
MetaRNN	Benign	0.37	T;T;T;T;T;T;T;T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Benign	1.8	.;.;.;L;.;.;L;.
PrimateAI	Uncertain	0.70	T
PROVEAN	Uncertain	-3.0	.;.;D;.;.;.;.;.
REVEL	Uncertain	0.44
Sift	Uncertain	0.0020	.;.;D;.;.;.;.;.
Sift4G	Uncertain	0.0030	D;T;D;D;.;D;D;D
Polyphen		0.77	P;.;P;P;D;D;P;.
Vest4		0.31
MutPred		0.56		.;.;.;Gain of phosphorylation at R1381 (P = 0.006);.;.;Gain of phosphorylation at R1381 (P = 0.006);.;
MVP		0.51
MPC		0.43
ClinPred		0.92	D
GERP RS		2.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.26
gMVP		0.51

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: rs727503226; hg19: chr19-50783614;