rs150593274

Positions:

• chr17-47221773-C-A
• chr17-47221773-C-T

Variant summary

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

The NM_002476.2(MYL4):​c.405C>A​(p.Phe135Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYL4 NM_002476.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59

Genes affected

MYL4 (HGNC:7585): (myosin light chain 4) Myosin is a hexameric ATPase cellular motor protein. It is composed of two myosin heavy chains, two nonphosphorylatable myosin alkali light chains, and two phosphorylatable myosin regulatory light chains. This gene encodes a myosin alkali light chain that is found in embryonic muscle and adult atria. Two alternatively spliced transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Jul 2008]

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=0.33373314).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL4	NM_002476.2	c.405C>A	p.Phe135Leu	missense_variant	4/7	ENST00000393450.5	NP_002467.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL4	ENST00000393450.5	c.405C>A	p.Phe135Leu	missense_variant	4/7	1	NM_002476.2	ENSP00000377096	P1

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	1.0
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Benign	9.1
DANN	Benign	0.94
DEOGEN2	Uncertain	0.62	D;D;T;.;D;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.066	N
LIST_S2	Uncertain	0.92	.;D;D;D;.;D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.33	T;T;T;T;T;T
MetaSVM	Uncertain	0.49	D
MutationAssessor	Benign	0.83	L;L;.;.;L;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-4.8	.;D;.;.;D;.
REVEL	Uncertain	0.46
Sift	Uncertain	0.012	.;D;.;.;D;.
Sift4G	Benign	0.097	T;T;T;T;T;D
Polyphen		1.0	D;D;.;.;D;.
Vest4		0.78
MutPred		0.56		Gain of disorder (P = 0.1531);Gain of disorder (P = 0.1531);Gain of disorder (P = 0.1531);Gain of disorder (P = 0.1531);Gain of disorder (P = 0.1531);.;
MVP		0.36
MPC		0.71
ClinPred		0.99	D
GERP RS		-11
Varity_R		0.47
gMVP		0.56

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: rs150593274; hg19: chr17-45299139;