rs5447

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002103.5(GYS1):c.1246A>G(p.Met416Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00969 in 1,613,926 control chromosomes in the GnomAD database, including 426 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.015 ( 67 hom., cov: 31)

Exomes 𝑓: 0.0092 ( 359 hom. )

Consequence

GYS1
NM_002103.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.35

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]

GYS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0027920902).

BP6

Variant 19-48977986-T-C is Benign according to our data. Variant chr19-48977986-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 329814.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-48977986-T-C is described in Lovd as [Benign]. Variant chr19-48977986-T-C is described in Lovd as [Likely_benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0925 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYS1	NM_002103.5 link	c.1246A>G	p.Met416Val	missense_variant	Exon 10 of 16	ENST00000323798.8	NP_002094.2	P13807-1
GYS1	NM_001161587.2 link	c.1054A>G	p.Met352Val	missense_variant	Exon 9 of 15		NP_001155059.1	P13807-2
GYS1	NR_027763.2 link	n.1261A>G		non_coding_transcript_exon_variant	Exon 9 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GYS1	ENST00000323798.8 link	c.1246A>G	p.Met416Val	missense_variant	Exon 10 of 16	1	NM_002103.5	ENSP00000317904.3	P13807-1
GYS1	ENST00000263276.6 link	c.1054A>G	p.Met352Val	missense_variant	Exon 9 of 15	1		ENSP00000263276.6	P13807-2
GYS1	ENST00000472004.5 link	n.1A>G		non_coding_transcript_exon_variant	Exon 1 of 4	3
GYS1	ENST00000496048.1 link	n.153A>G		non_coding_transcript_exon_variant	Exon 2 of 5	3

Frequencies

GnomAD3 genomes

AF:

0.0148

AC:

2253

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0143

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00433

Gnomad EAS

AF:

0.0994

Gnomad SAS

AF:

0.0211

Gnomad FIN

AF:

0.0616

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00451

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0190

AC:

4768

AN:

251470

Hom.:

167

AF XY:

0.0185

AC XY:

2511

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.0138

Gnomad AMR exome

AF:

0.00240

Gnomad ASJ exome

AF:

0.00456

Gnomad EAS exome

AF:

0.106

Gnomad SAS exome

AF:

0.0179

Gnomad FIN exome

AF:

0.0593

Gnomad NFE exome

AF:

0.00468

Gnomad OTH exome

AF:

0.0160

GnomAD4 exome

AF:

0.00915

AC:

13378

AN:

1461768

Hom.:

359

Cov.:

AF XY:

0.00948

AC XY:

6891

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0134

Gnomad4 AMR exome

AF:

0.00228

Gnomad4 ASJ exome

AF:

0.00406

Gnomad4 EAS exome

AF:

0.103

Gnomad4 SAS exome

AF:

0.0192

Gnomad4 FIN exome

AF:

0.0563

Gnomad4 NFE exome

AF:

0.00293

Gnomad4 OTH exome

AF:

0.0111

GnomAD4 genome

AF:

0.0149

AC:

2265

AN:

152158

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

1339

AN XY:

74376

show subpopulations

Gnomad4 AFR

AF:

0.0143

Gnomad4 AMR

AF:

0.00295

Gnomad4 ASJ

AF:

0.00433

Gnomad4 EAS

AF:

0.0997

Gnomad4 SAS

AF:

0.0214

Gnomad4 FIN

AF:

0.0616

Gnomad4 NFE

AF:

0.00451

Gnomad4 OTH

AF:

0.0152

Alfa

AF:

0.00808

Hom.:

Bravo

AF:

0.0107

TwinsUK

AF:

0.00162

AC:

ALSPAC

AF:

0.00519

AC:

ESP6500AA

AF:

0.0145

AC:

ESP6500EA

AF:

0.00360

AC:

ExAC

AF:

0.0187

AC:

2274

Asia WGS

AF:

0.0530

AC:

183

AN:

3478

EpiCase

AF:

0.00245

EpiControl

AF:

0.00261

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Aug 17, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jun 06, 2016

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Glycogen storage disease due to muscle and heart glycogen synthase deficiency

Benign:2

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.34

T;.

Eigen

Benign

-0.17

Eigen_PC

Benign

0.0093

FATHMM_MKL

Uncertain

0.78

LIST_S2

Uncertain

0.88

D;D

MetaRNN

Benign

0.0028

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.46

N;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.89

N;N

REVEL

Benign

0.13

Sift

Benign

0.27

T;T

Sift4G

Benign

0.29

T;T

Polyphen

0.0040

B;.

Vest4

0.055

MPC

0.49

ClinPred

0.0079

GERP RS

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.41

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