rs5453

Variant summary

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

The NM_002103.5(GYS1):​c.2071C>G​(p.Pro691Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: not found (cov: 32)

Consequence

GYS1
NM_002103.5 missense

Scores

9
10

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.51
Variant links:
Genes affected
GYS1 (HGNC:4706): (glycogen synthase 1) The protein encoded by this gene catalyzes the addition of glucose monomers to the growing glycogen molecule through the formation of alpha-1,4-glycoside linkages. Mutations in this gene are associated with muscle glycogen storage disease. Alternatively spliced transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Sep 2009]

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=0.25684416).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
GYS1NM_002103.5 linkuse as main transcriptc.2071C>G p.Pro691Ala missense_variant 16/16 ENST00000323798.8 NP_002094.2 P13807-1
GYS1NM_001161587.2 linkuse as main transcriptc.1879C>G p.Pro627Ala missense_variant 15/15 NP_001155059.1 P13807-2
GYS1NR_027763.2 linkuse as main transcriptn.2086C>G non_coding_transcript_exon_variant 15/15

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
GYS1ENST00000323798.8 linkuse as main transcriptc.2071C>G p.Pro691Ala missense_variant 16/161 NM_002103.5 ENSP00000317904.3 P13807-1
GYS1ENST00000263276.6 linkuse as main transcriptc.1879C>G p.Pro627Ala missense_variant 15/151 ENSP00000263276.6 P13807-2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.090
BayesDel_addAF
Uncertain
0.013
T
BayesDel_noAF
Benign
-0.22
CADD
Benign
22
DANN
Uncertain
0.99
DEOGEN2
Uncertain
0.46
T;.
Eigen
Benign
-0.058
Eigen_PC
Benign
0.11
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.035
D
MetaRNN
Benign
0.26
T;T
MetaSVM
Benign
-0.70
T
MutationAssessor
Uncertain
2.2
M;.
PrimateAI
Uncertain
0.73
T
PROVEAN
Benign
-2.0
N;N
REVEL
Benign
0.18
Sift
Uncertain
0.015
D;D
Sift4G
Uncertain
0.027
D;D
Polyphen
0.16
B;.
Vest4
0.26
MutPred
0.077
Gain of helix (P = 0.0022);.;
MVP
0.71
MPC
0.53
ClinPred
0.82
D
GERP RS
5.6
Varity_R
0.14
gMVP
0.59

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: rs5453; hg19: chr19-49472688; API