Variant 19-48968838-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_002103.5(GYS1):c.*450G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00224 in 459,378 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0021 ( 7 hom., cov: 32)

Exomes 𝑓: 0.0023 ( 15 hom. )

Consequence

GYS1
NM_002103.5 3_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.372

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 (BayesDel_noAF=-0.82).

BP6

Variant 19-48968838-C-T is Benign according to our data. Variant chr19-48968838-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 329799.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00207 (315/152348) while in subpopulation EAS AF= 0.0435 (225/5172). AF 95% confidence interval is 0.0388. There are 7 homozygotes in gnomad4. There are 163 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
GYS1	NM_002103.5 linkuse as main transcript	c.*450G>A	3_prime_UTR_variant	16/16	ENST00000323798.8
GYS1	NM_001161587.2 linkuse as main transcript	c.*450G>A	3_prime_UTR_variant	15/15
GYS1	NR_027763.2 linkuse as main transcript	n.2679G>A	non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYS1	ENST00000323798.8 linkuse as main transcript	c.*450G>A		3_prime_UTR_variant	16/16	1	NM_002103.5	P1	P13807-1
GYS1	ENST00000263276.6 linkuse as main transcript	c.*450G>A		3_prime_UTR_variant	15/15	1			P13807-2

Frequencies

GnomAD3 genomes

AF:

0.00208

AC:

316

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.0434

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.000376

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00414

AC:

542

AN:

131056

Hom.:

AF XY:

0.00378

AC XY:

270

AN XY:

71506

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000246

Gnomad ASJ exome

AF:

0.0113

Gnomad EAS exome

AF:

0.0378

Gnomad SAS exome

AF:

0.000670

Gnomad FIN exome

AF:

0.000928

Gnomad NFE exome

AF:

0.000378

Gnomad OTH exome

AF:

0.00274

GnomAD4 exome

AF:

0.00232

AC:

712

AN:

307030

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

396

AN XY:

174652

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000256

Gnomad4 ASJ exome

AF:

0.0129

Gnomad4 EAS exome

AF:

0.0424

Gnomad4 SAS exome

AF:

0.000754

Gnomad4 FIN exome

AF:

0.000717

Gnomad4 NFE exome

AF:

0.000394

Gnomad4 OTH exome

AF:

0.00326

GnomAD4 genome

AF:

0.00207

AC:

315

AN:

152348

Hom.:

Cov.:

AF XY:

0.00219

AC XY:

163

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000653

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.0435

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.000376

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00188

Hom.:

Bravo

AF:

0.00224

Asia WGS

AF:

0.0200

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Hereditary hyperferritinemia with congenital cataracts

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Neuroferritinopathy

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Glycogen storage disease due to muscle and heart glycogen synthase deficiency

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 24, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.42

DANN

Benign

0.75

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