2-210298513-T-A

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

2
17

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]

Genome browser will be placed here

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
MYL1NM_079420.3 linkuse as main transcriptc.211A>T p.Thr71Ser missense_variant 3/7 ENST00000352451.4
MYL1NM_079422.3 linkuse as main transcriptc.79A>T p.Thr27Ser missense_variant 3/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYL1ENST00000352451.4 linkuse as main transcriptc.211A>T p.Thr71Ser missense_variant 3/71 NM_079420.3 P05976-1
MYL1ENST00000341685.8 linkuse as main transcriptc.79A>T p.Thr27Ser missense_variant 3/71 P1P05976-2
MYL1ENST00000484290.1 linkuse as main transcriptn.342A>T non_coding_transcript_exon_variant 4/65
MYL1ENST00000496436.5 linkuse as main transcriptn.314A>T non_coding_transcript_exon_variant 3/65

Frequencies

GnomAD3 genomes
AF:
0.000112
AC:
17
AN:
152150
Hom.:
0
Cov.:
32
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:
16
AN:
251270
Hom.:
0
AF XY:
0.0000295
AC XY:
4
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.:
0
Cov.:
32
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:
17
AN:
152150
Hom.:
0
Cov.:
32
AF XY:
0.000108
AC XY:
8
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.:
0
Bravo
AF:
0.0000982
TwinsUK
AF:
0.000270
AC:
1
ALSPAC
AF:
0.000259
AC:
1
ExAC
AF:
0.0000659
AC:
8

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 submitterclinical testingAmbry GeneticsDec 18, 2023The 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
T
BayesDel_noAF
Benign
-0.52
CADD
Benign
19
DANN
Benign
0.94
DEOGEN2
Benign
0.25
.;T
Eigen
Benign
-0.36
Eigen_PC
Benign
-0.12
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Benign
0.74
T;T
M_CAP
Benign
0.0095
T
MetaRNN
Benign
0.13
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.015
.;N
MutationTaster
Benign
0.85
N;N
PrimateAI
Uncertain
0.53
T
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
T
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.

Other links and lift over

dbSNP: rs145897731; hg19: chr2-211163237; API