Variant 19-48968380-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.*908G>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 0.0128 in 454,380 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0076 ( 10 hom., cov: 32)

Exomes 𝑓: 0.015 ( 82 hom. )

Consequence

GYS1
NM_002103.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.600

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:

GYS1 (HGNC:):

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=-0.51).

BP6

Variant 19-48968380-C-T is Benign according to our data. Variant chr19-48968380-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 329792.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 = 0.00759 (1155/152144) while in subpopulation SAS AF= 0.038 (183/4822). AF 95% confidence interval is 0.0335. There are 10 homozygotes in gnomad4. There are 634 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 10 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein	UniProt
GYS1	NM_002103.5 linkuse as main transcript	c.*908G>A	3_prime_UTR_variant	16/16	ENST00000323798.8	NP_002094.2	P13807-1
GYS1	NM_001161587.2 linkuse as main transcript	c.*908G>A	3_prime_UTR_variant	15/15		NP_001155059.1	P13807-2
GYS1	NR_027763.2 linkuse as main transcript	n.3137G>A	non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYS1	ENST00000323798 linkuse as main transcript	c.*908G>A		3_prime_UTR_variant	16/16	1	NM_002103.5	ENSP00000317904.3		P13807-1
GYS1	ENST00000263276 linkuse as main transcript	c.*908G>A		3_prime_UTR_variant	15/15	1		ENSP00000263276.6		P13807-2

Frequencies

GnomAD3 genomes

AF:

0.00760

AC:

1156

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00167

Gnomad AMI

AF:

0.00771

Gnomad AMR

AF:

0.00295

Gnomad ASJ

AF:

0.00461

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0381

Gnomad FIN

AF:

0.0187

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00916

Gnomad OTH

AF:

0.00622

GnomAD3 exomes

AF:

0.0129

AC:

1768

AN:

136628

Hom.:

AF XY:

0.0157

AC XY:

1163

AN XY:

74178

show subpopulations

Gnomad AFR exome

AF:

0.00186

Gnomad AMR exome

AF:

0.00388

Gnomad ASJ exome

AF:

0.00686

Gnomad EAS exome

AF:

0.0000952

Gnomad SAS exome

AF:

0.0414

Gnomad FIN exome

AF:

0.0170

Gnomad NFE exome

AF:

0.00990

Gnomad OTH exome

AF:

0.00890

GnomAD4 exome

AF:

0.0154

AC:

4651

AN:

302236

Hom.:

Cov.:

AF XY:

0.0180

AC XY:

3093

AN XY:

172256

show subpopulations

Gnomad4 AFR exome

AF:

0.00140

Gnomad4 AMR exome

AF:

0.00389

Gnomad4 ASJ exome

AF:

0.00658

Gnomad4 EAS exome

AF:

0.000109

Gnomad4 SAS exome

AF:

0.0407

Gnomad4 FIN exome

AF:

0.0168

Gnomad4 NFE exome

AF:

0.0104

Gnomad4 OTH exome

AF:

0.0112

GnomAD4 genome

AF:

0.00759

AC:

1155

AN:

152144

Hom.:

Cov.:

AF XY:

0.00853

AC XY:

634

AN XY:

74346

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00295

Gnomad4 ASJ

AF:

0.00461

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0380

Gnomad4 FIN

AF:

0.0187

Gnomad4 NFE

AF:

0.00916

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00866

Hom.:

Bravo

AF:

0.00590

Asia WGS

AF:

0.0120

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 20, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

6.9

DANN

Benign

0.72

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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