Genetic Variant GYS1:c.1810-314C>T (chr19-48970169-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_002103.5(GYS1):c.1810-314C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0459 in 479,504 control chromosomes in the GnomAD database, including 686 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.044 ( 216 hom., cov: 32)

Exomes 𝑓: 0.047 ( 470 hom. )

Consequence

GYS1
NM_002103.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.838

Publications

3 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0613 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
GYS1	NM_002103.5 link	c.1810-314C>T	intron_variant	Intron 14 of 15	ENST00000323798.8	NP_002094.2
GYS1	NM_001161587.2 link	c.1618-314C>T	intron_variant	Intron 13 of 14		NP_001155059.1
GYS1	NR_027763.2 link	n.1825-314C>T	intron_variant	Intron 13 of 14

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
GYS1	ENST00000323798.8 link	c.1810-314C>T	intron_variant	Intron 14 of 15	1	NM_002103.5	ENSP00000317904.3
GYS1	ENST00000263276.6 link	c.1618-314C>T	intron_variant	Intron 13 of 14	1		ENSP00000263276.6
GYS1	ENST00000594220.1 link	c.*200C>T	downstream_gene_variant		6		ENSP00000470072.1

Frequencies

GnomAD3 genomes

AF:

0.0444

AC:

6748

AN:

151976

Hom.:

214

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0115

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0644

Gnomad ASJ

AF:

0.0288

Gnomad EAS

AF:

0.00135

Gnomad SAS

AF:

0.0359

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.0541

Gnomad OTH

AF:

0.0392

GnomAD4 exome

AF:

0.0466

AC:

15248

AN:

327410

Hom.:

470

AF XY:

0.0451

AC XY:

7799

AN XY:

173082

show subpopulations

African (AFR)

AF:

0.0122

AC:

122

AN:

9986

American (AMR)

AF:

0.0624

AC:

842

AN:

13488

Ashkenazi Jewish (ASJ)

AF:

0.0246

AC:

251

AN:

10220

East Asian (EAS)

AF:

0.000353

AC:

AN:

19858

South Asian (SAS)

AF:

0.0308

AC:

1263

AN:

40996

European-Finnish (FIN)

AF:

0.103

AC:

1763

AN:

17160

Middle Eastern (MID)

AF:

0.0114

AC:

AN:

1408

European-Non Finnish (NFE)

AF:

0.0520

AC:

10174

AN:

195588

Other (OTH)

AF:

0.0433

AC:

810

AN:

18706

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

697

1394

2091

2788

3485

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

162

216

270

<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:

0.0444

AC:

6756

AN:

152094

Hom.:

216

Cov.:

AF XY:

0.0479

AC XY:

3561

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.0115

AC:

479

AN:

41514

American (AMR)

AF:

0.0646

AC:

986

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.0288

AC:

100

AN:

3472

East Asian (EAS)

AF:

0.00135

AC:

AN:

5178

South Asian (SAS)

AF:

0.0357

AC:

172

AN:

4820

European-Finnish (FIN)

AF:

0.118

AC:

1242

AN:

10546

Middle Eastern (MID)

AF:

0.0170

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0541

AC:

3681

AN:

67982

Other (OTH)

AF:

0.0388

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

322

644

966

1288

1610

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

164

246

328

410

<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:

0.0432

Hom.:

291

Bravo

AF:

0.0383

Asia WGS

AF:

0.0180

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.29

(source)

DANN

Benign

0.67

PhyloP100

-0.84

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over