NM_014981.3:c.5623G>C

Variant names:

• chr3-108384695-C-G
• rs370570528
• NM_014981.3:c.5623G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_014981.3(MYH15):​c.5623G>C​(p.Glu1875Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYH15 NM_014981.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.62

Genes affected

MYH15 (HGNC:31073): (myosin heavy chain 15) Predicted to enable several functions, including ATP binding activity; actin filament binding activity; and calmodulin binding activity. Predicted to be involved in extraocular skeletal muscle development. Located in cytosol and intracellular membrane-bounded organelle. [provided by Alliance of Genome Resources, Apr 2022]

LOC124900545 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.898

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH15	NM_014981.3	c.5623G>C	p.Glu1875Gln	missense_variant	Exon 39 of 41	ENST00000693548.1	NP_055796.2
MYH15	XM_011512559.3	c.5683G>C	p.Glu1895Gln	missense_variant	Exon 41 of 43		XP_011510861.1
LOC124900545	XR_007095998.1	n.113-2285C>G		intron_variant	Intron 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH15	ENST00000693548.1	c.5623G>C	p.Glu1875Gln	missense_variant	Exon 39 of 41		NM_014981.3	ENSP00000508967.1
MYH15	ENST00000273353.5	c.5623G>C	p.Glu1875Gln	missense_variant	Exon 40 of 42	1		ENSP00000273353.4
MYH15	ENST00000689784.1	c.4642G>C	p.Glu1548Gln	missense_variant	Exon 31 of 33			ENSP00000509841.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.38	T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.47
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.011	T
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.55	D
MutationAssessor	Uncertain	2.7	M
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.5	N
REVEL	Uncertain	0.60
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.64
MutPred		0.65		Gain of MoRF binding (P = 0.0214);
MVP		0.96
MPC		0.44
ClinPred		0.97	D
GERP RS		5.6
Varity_R		0.22
gMVP		0.25

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: rs370570528; hg19: chr3-108103542;