Variant chr2-210298513-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM2BP4_Moderate

The NM_079420.3(MYL1):c.211A>T(p.Thr71Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000226 in 1,613,938 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 0 hom. )

Consequence

MYL1
NM_079420.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.938

Variant links:

Genes affected

MYL1 (HGNC:7582): (myosin light chain 1) Myosin is a hexameric ATPase cellular motor protein. It is composed of two heavy chains, two nonphosphorylatable alkali light chains, and two phosphorylatable regulatory light chains. This gene encodes a myosin alkali light chain expressed in fast skeletal muscle. Two transcript variants have been identified for this gene. [provided by RefSeq, Jul 2008]

MYL1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM1

In a modified_residue Phosphothreonine (size 0) in uniprot entity MYL1_HUMAN

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12550274).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MYL1	NM_079420.3 linkuse as main transcript	c.211A>T	p.Thr71Ser	missense_variant	3/7	ENST00000352451.4
MYL1	NM_079422.3 linkuse as main transcript	c.79A>T	p.Thr27Ser	missense_variant	3/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MYL1	ENST00000352451.4 linkuse as main transcript	c.211A>T	p.Thr71Ser	missense_variant	3/7	1	NM_079420.3		P05976-1
MYL1	ENST00000341685.8 linkuse as main transcript	c.79A>T	p.Thr27Ser	missense_variant	3/7	1		P1	P05976-2
MYL1	ENST00000484290.1 linkuse as main transcript	n.342A>T		non_coding_transcript_exon_variant	4/6	5
MYL1	ENST00000496436.5 linkuse as main transcript	n.314A>T		non_coding_transcript_exon_variant	3/6	5

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

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:

0.000221

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000637

AC:

AN:

251270

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.000132

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000237

AC:

347

AN:

1461788

Hom.:

Cov.:

AF XY:

0.000235

AC XY:

171

AN XY:

727192

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.0000187

Gnomad4 NFE exome

AF:

0.000309

Gnomad4 OTH exome

AF:

0.0000331

GnomAD4 genome

AF:

0.000112

AC:

AN:

152150

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74316

show subpopulations

Gnomad4 AFR

AF:

0.0000483

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:

0.000221

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000248

Hom.:

Bravo

AF:

0.0000982

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000659

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

Dec 18, 2023

The c.211A>T (p.T71S) alteration is located in exon 3 (coding exon 3) of the MYL1 gene. This alteration results from a A to T substitution at nucleotide position 211, causing the threonine (T) at amino acid position 71 to be replaced by a serine (S). 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

0.16

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.94

DEOGEN2

Benign

0.25

.;T

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.12

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.0095

MetaRNN

Benign

0.13

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.015

.;N

MutationTaster

Benign

0.85

N;N

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.099

Sift

Benign

0.46

T;T

Sift4G

Benign

0.74

T;T

Polyphen

0.0

B;B

Vest4

0.34

MutPred

0.33

.;Gain of disorder (P = 0.0504);

MVP

0.63

MPC

0.072

ClinPred

0.093

GERP RS

5.2

Varity_R

0.10

gMVP

0.36

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