chr19-48970606-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_002103.5(GYS1):c.1749C>T(p.Ile583Ile) variant causes a synonymous change. The variant allele was found at a frequency of 0.00038 in 1,613,966 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. I583I) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00028 ( 2 hom., cov: 31)

Exomes 𝑓: 0.00039 ( 5 hom. )

Consequence

GYS1
NM_002103.5 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 4.71

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

glycogen storage disease due to muscle and heart glycogen synthase deficiency
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen, Genomics England PanelApp, Orphanet

GYS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.38).

BP6

Variant 19-48970606-G-A is Benign according to our data. Variant chr19-48970606-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 725380.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. GnomAd4 allele frequency = 0.000282 (43/152314) while in subpopulation SAS AF = 0.0089 (43/4834). AF 95% confidence interval is 0.00679. There are 2 homozygotes in GnomAd4. There are 36 alleles in the male GnomAd4 subpopulation. Median coverage is 31. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GYS1	NM_002103.5 link	c.1749C>T	p.Ile583Ile	synonymous_variant	Exon 14 of 16	ENST00000323798.8	NP_002094.2	P13807-1
GYS1	NM_001161587.2 link	c.1557C>T	p.Ile519Ile	synonymous_variant	Exon 13 of 15		NP_001155059.1	P13807-2
GYS1	NR_027763.2 link	n.1764C>T		non_coding_transcript_exon_variant	Exon 13 of 15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GYS1	ENST00000323798.8 link	c.1749C>T	p.Ile583Ile	synonymous_variant	Exon 14 of 16	1	NM_002103.5	ENSP00000317904.3	P13807-1
GYS1	ENST00000263276.6 link	c.1557C>T	p.Ile519Ile	synonymous_variant	Exon 13 of 15	1		ENSP00000263276.6	P13807-2
GYS1	ENST00000594220.1 link	c.102C>T	p.Ile34Ile	synonymous_variant	Exon 1 of 1	6		ENSP00000470072.1	M0QYU1
GYS1	ENST00000472004.5 link	n.*144C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000283

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00889

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000809

AC:

203

AN:

250860

AF XY:

0.00108

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000390

AC:

570

AN:

1461652

Hom.:

Cov.:

AF XY:

0.000572

AC XY:

416

AN XY:

727120

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33472

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00629

AC:

542

AN:

86236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53372

Middle Eastern (MID)

AF:

0.000698

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111906

Other (OTH)

AF:

0.000364

AC:

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

133

177

221

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000282

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000483

AC XY:

AN XY:

74480

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41558

American (AMR)

AF:

0.00

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00890

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000529

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Aug 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

GYS1: BP4, BS2 -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Glycogen storage disease due to muscle and heart glycogen synthase deficiency

Benign:1

Dec 05, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

4.7

PromoterAI

-0.055

Neutral

(source)

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over