rs12610591

chr19-50301720-C-Gchr19-50301720-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.5529C>G(p.Ser1843Arg) variant causes a missense 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. 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. Synonymous variant affecting the same amino acid position (i.e. S1843S) has been classified as Benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYH14 NM_001145809.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.00

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=0.22031298).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYH14	NM_001145809.2	c.5529C>G	p.Ser1843Arg	missense_variant	40/43	ENST00000642316.2
MYH14	NM_001077186.2	c.5430C>G	p.Ser1810Arg	missense_variant	39/42
MYH14	NM_024729.4	c.5406C>G	p.Ser1802Arg	missense_variant	38/41

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYH14	ENST00000642316.2	c.5529C>G	p.Ser1843Arg	missense_variant	40/43		NM_001145809.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.83
BayesDel_addAF	Benign	-0.049	T
BayesDel_noAF	Benign	-0.31
Cadd	Benign	8.3
Dann	Uncertain	1.0
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.11	N
M_CAP	Benign	0.054	D
MetaRNN	Benign	0.22	T;T;T;T;T;T;T
MetaSVM	Benign	-0.56	T
MutationTaster	Benign	0.96	D;D;D;D
PrimateAI	Uncertain	0.69	T
Sift4G	Benign	0.86	T;T;T;T;.;T;T
Polyphen		0.98	D;.;D;D;D;D;D
Vest4		0.36
MutPred		0.31		.;.;.;Loss of phosphorylation at S1802 (P = 0.0161);.;.;Loss of phosphorylation at S1802 (P = 0.0161);
MVP		0.77
MPC		0.63
ClinPred		0.84	D
GERP RS		-0.92
Varity_R		0.10
gMVP		0.26

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: rs12610591; hg19: chr19-50804977;