2-210298498-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_079420.3(MYL1):​c.226G>A​(p.Gly76Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000473 in 1,614,044 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00050 ( 1 hom. )

Consequence

MYL1
NM_079420.3 missense

Scores

5
10
4

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.91
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 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.40723523).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
MYL1NM_079420.3 linkuse as main transcriptc.226G>A p.Gly76Ser missense_variant 3/7 ENST00000352451.4
MYL1NM_079422.3 linkuse as main transcriptc.94G>A p.Gly32Ser missense_variant 3/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MYL1ENST00000352451.4 linkuse as main transcriptc.226G>A p.Gly76Ser missense_variant 3/71 NM_079420.3 P05976-1
MYL1ENST00000341685.8 linkuse as main transcriptc.94G>A p.Gly32Ser missense_variant 3/71 P1P05976-2
MYL1ENST00000484290.1 linkuse as main transcriptn.357G>A non_coding_transcript_exon_variant 4/65
MYL1ENST00000496436.5 linkuse as main transcriptn.329G>A non_coding_transcript_exon_variant 3/65

Frequencies

GnomAD3 genomes
AF:
0.000243
AC:
37
AN:
152102
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000966
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000262
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000412
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000195
AC:
49
AN:
251334
Hom.:
0
AF XY:
0.000243
AC XY:
33
AN XY:
135830
show subpopulations
Gnomad AFR exome
AF:
0.000123
Gnomad AMR exome
AF:
0.000116
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000369
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000497
AC:
726
AN:
1461824
Hom.:
1
Cov.:
32
AF XY:
0.000472
AC XY:
343
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000139
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000607
Gnomad4 OTH exome
AF:
0.000497
GnomAD4 genome
AF:
0.000243
AC:
37
AN:
152220
Hom.:
0
Cov.:
32
AF XY:
0.000242
AC XY:
18
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.0000963
Gnomad4 AMR
AF:
0.000262
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000412
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000443
Hom.:
0
Bravo
AF:
0.000268
TwinsUK
AF:
0.000539
AC:
2
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00105
AC:
9
ExAC
AF:
0.000214
AC:
26
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.000382
EpiControl
AF:
0.000356

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenJul 01, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.78
BayesDel_addAF
Benign
-0.16
T
BayesDel_noAF
Benign
-0.16
CADD
Pathogenic
33
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.69
.;D
Eigen
Pathogenic
0.88
Eigen_PC
Pathogenic
0.83
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Pathogenic
0.99
D;D
M_CAP
Uncertain
0.094
D
MetaRNN
Benign
0.41
T;T
MetaSVM
Uncertain
0.20
D
MutationAssessor
Uncertain
2.4
.;M
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.61
T
PROVEAN
Uncertain
-4.2
D;D
REVEL
Uncertain
0.54
Sift
Uncertain
0.0010
D;D
Sift4G
Uncertain
0.020
D;D
Polyphen
1.0
D;D
Vest4
0.61
MVP
0.87
MPC
0.41
ClinPred
0.80
D
GERP RS
5.2
Varity_R
0.71
gMVP
0.59

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.16
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: rs199843326; hg19: chr2-211163222; COSMIC: COSV58977123; API