Variant 4-681930-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002477.2(MYL5):c.458C>T(p.Ala153Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000179 in 1,325,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00019 ( 0 hom. )

Consequence

MYL5
NM_002477.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.33

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10435128).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MYL5	NM_002477.2 link	c.458C>T	p.Ala153Val	missense_variant	9/9	ENST00000400159.7	NP_002468.1	Q02045-1
SLC49A3	NM_032219.4 link	c.*28G>A		3_prime_UTR_variant	10/10	ENST00000322224.9	NP_115595.2	Q6UXD7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MYL5	ENST00000400159.7 link	c.458C>T	p.Ala153Val	missense_variant	9/9	1	NM_002477.2	ENSP00000383023.2		Q02045-1
SLC49A3	ENST00000322224 link	c.*28G>A		3_prime_UTR_variant	10/10	1	NM_032219.4	ENSP00000320234.4		Q6UXD7-2

Frequencies

GnomAD3 genomes

AF:

0.0000856

AC:

AN:

151948

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000242

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000388

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000736

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000150

AC:

AN:

113312

Hom.:

AF XY:

0.000179

AC XY:

AN XY:

61288

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000307

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000266

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000149

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000191

AC:

224

AN:

1173876

Hom.:

Cov.:

AF XY:

0.000223

AC XY:

126

AN XY:

565028

show subpopulations

Gnomad4 AFR exome

AF:

0.0000802

Gnomad4 AMR exome

AF:

0.000230

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000985

Gnomad4 SAS exome

AF:

0.000231

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000209

Gnomad4 OTH exome

AF:

0.0000857

GnomAD4 genome

AF:

0.0000855

AC:

AN:

152058

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000389

Gnomad4 SAS

AF:

0.000830

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000736

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000164

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.000143

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

Mar 07, 2024

The c.458C>T (p.A153V) 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 458, causing the alanine (A) at amino acid position 153 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

0.15

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.34

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

.;.;.;T

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.52

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.76

.;.;T;T

M_CAP

Benign

0.039

MetaRNN

Benign

0.10

T;T;T;T

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.6

.;.;.;M

PrimateAI

Uncertain

0.48

PROVEAN

Benign

-2.3

N;N;N;N

REVEL

Benign

0.081

Sift

Benign

0.088

T;T;T;T

Sift4G

Benign

0.25

T;T;T;T

Polyphen

0.23

.;.;.;B

Vest4

0.23

MutPred

0.42

.;.;.;Loss of helix (P = 0.2022);

MVP

0.56

MPC

0.032

ClinPred

0.051

GERP RS

2.5

Varity_R

0.047

gMVP

0.19

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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