rs150593274

Variant names:

• chr17-47221773-C-A
• rs150593274
• NM_002476.2:c.405C>A

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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. Synonymous variant affecting the same amino acid position (i.e. F135F) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MYL4 NM_002476.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.59
• Publications: 1 publications found

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]

MYL4 Gene-Disease associations (from GenCC):

• atrial fibrillation, familial, 18

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• familial atrial fibrillation

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33373314).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002476.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL4	NM_002476.2	MANE Select	c.405C>A	p.Phe135Leu	missense	Exon 4 of 7	NP_002467.1
	MYL4	NM_001002841.2		c.405C>A	p.Phe135Leu	missense	Exon 5 of 8	NP_001002841.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MYL4	ENST00000393450.5	TSL:1 MANE Select	c.405C>A	p.Phe135Leu	missense	Exon 4 of 7	ENSP00000377096.1
	MYL4	ENST00000954741.1		c.405C>A	p.Phe135Leu	missense	Exon 4 of 7	ENSP00000624800.1
	MYL4	ENST00000954746.1		c.405C>A	p.Phe135Leu	missense	Exon 5 of 8	ENSP00000624805.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.066	N
LIST_S2	Uncertain	0.92	D
M_CAP	Benign	0.038	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	0.49	D
MutationAssessor	Benign	0.83	L
PhyloP100		-2.6
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-4.8	D
REVEL	Uncertain	0.46
Sift	Uncertain	0.012	D
Sift4G	Benign	0.097	T
Polyphen		1.0	D
Vest4		0.78
MutPred		0.56		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

Other links and lift over

dbSNP: rs150593274; hg19: chr17-45299139;