Variant 4-681951-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_002477.2(MYL5):c.479C>T(p.Ala160Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000237 in 1,351,882 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000014 ( 0 hom. )

Consequence

MYL5
NM_002477.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.166

Variant links:

Genes affected

MYL5 (HGNC:7586): (myosin light chain 5) This gene encodes one of the myosin light chains, a component of the hexameric ATPase cellular motor protein myosin. Myosin is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene product, one of the regulatory light chains, is expressed in fetal muscle and in adult retina, cerebellum, and basal ganglia. [provided by RefSeq, Jul 2008]

MYL5 links:

SLC49A3 (HGNC:26177): (solute carrier family 49 member 3) Predicted to enable transmembrane transporter activity. Predicted to be involved in transmembrane transport. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SLC49A3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06511888).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL5	NM_002477.2 linkuse as main transcript	c.479C>T	p.Ala160Val	missense_variant	9/9	ENST00000400159.7
SLC49A3	NM_032219.4 linkuse as main transcript	c.*7G>A		3_prime_UTR_variant	10/10	ENST00000322224.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL5	ENST00000400159.7 linkuse as main transcript	c.479C>T	p.Ala160Val	missense_variant	9/9	1	NM_002477.2	P1	Q02045-1
SLC49A3	ENST00000322224.9 linkuse as main transcript	c.*7G>A		3_prime_UTR_variant	10/10	1	NM_032219.4	P4	Q6UXD7-2

Frequencies

GnomAD3 genomes

AF:

0.0000986

AC:

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.000481

GnomAD3 exomes

AF:

0.0000257

AC:

AN:

116556

Hom.:

AF XY:

0.0000475

AC XY:

AN XY:

63170

show subpopulations

Gnomad AFR exome

AF:

0.000110

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000326

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000142

AC:

AN:

1199720

Hom.:

Cov.:

AF XY:

0.0000103

AC XY:

AN XY:

580820

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000462

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000926

Gnomad4 OTH exome

AF:

0.0000629

GnomAD4 genome

AF:

0.0000986

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.000476

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000756

ESP6500AA

AF:

0.000456

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000418

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2021

The c.479C>T (p.A160V) alteration is located in exon 7 (coding exon 7) of the MYL5 gene. This alteration results from a C to T substitution at nucleotide position 479, causing the alanine (A) at amino acid position 160 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.39

Cadd

Benign

Dann

Uncertain

1.0

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.10

M_CAP

Uncertain

0.099

MetaRNN

Benign

0.065

T;T;T;T

MetaSVM

Benign

-0.69

MutationTaster

Benign

1.0

D;D;D;D;D;N;N;N;N

PrimateAI

Benign

0.39

PROVEAN

Uncertain

-2.4

N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.067

T;T;T;T

Sift4G

Benign

0.16

T;T;T;T

Polyphen

0.023

.;.;.;B

Vest4

0.12

MVP

0.60

MPC

0.070

ClinPred

0.090

GERP RS

1.5

Varity_R

0.068

gMVP

0.16

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over