rs16941677

chr17-47222448-A-Gchr17-47222448-A-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_002476.2(MYL4):c.556A>G(p.Asn186Asp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,840 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N186Y) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: MYL4 NM_002476.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.33

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL4	NM_002476.2	c.556A>G	p.Asn186Asp	missense_variant	5/7	ENST00000393450.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL4	ENST00000393450.5	c.556A>G	p.Asn186Asp	missense_variant	5/7	1	NM_002476.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461840 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727232

Gnomad4 AFR exome AF: 0.0000299

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

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
Cadd	Uncertain	25
Dann	Uncertain	1.0
DEOGEN2	Uncertain	0.63	D;D;.;D
Eigen	Uncertain	0.44
Eigen_PC	Uncertain	0.46
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.058	D
MetaRNN	Uncertain	0.72	D;D;D;D
MetaSVM	Uncertain	-0.090	T
MutationAssessor	Uncertain	2.1	M;M;.;M
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.78	T
Sift4G	Benign	0.075	T;T;T;T
Polyphen		0.76	P;P;.;P
Vest4		0.72
MutPred		0.46		Gain of catalytic residue at N186 (P = 0.0466);Gain of catalytic residue at N186 (P = 0.0466);Gain of catalytic residue at N186 (P = 0.0466);Gain of catalytic residue at N186 (P = 0.0466);
MVP		0.92
MPC		0.52
ClinPred		0.99	D
GERP RS		4.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.56
gMVP		0.41

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: rs16941677; hg19: chr17-45299814; COSMIC: COSV61698574; COSMIC: COSV61698574;