Variant 19-48968987-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_ModerateBP6BS1BS2

The NM_002103.5(GYS1):c.*301G>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 0.00281 in 611,936 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0019 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 12 hom. )

Consequence

GYS1
NM_002103.5 3_prime_UTR

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:2

Conservation

PhyloP100: 0.249

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BP6

Variant 19-48968987-C-T is Benign according to our data. Variant chr19-48968987-C-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 329801.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=1, Likely_benign=2}.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00185 (282/152346) while in subpopulation SAS AF= 0.00704 (34/4832). AF 95% confidence interval is 0.00518. There are 1 homozygotes in gnomad4. There are 146 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 12 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
GYS1	NM_002103.5 linkuse as main transcript	c.*301G>A	3_prime_UTR_variant	16/16	ENST00000323798.8
GYS1	NM_001161587.2 linkuse as main transcript	c.*301G>A	3_prime_UTR_variant	15/15
GYS1	NR_027763.2 linkuse as main transcript	n.2530G>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.*301G>A		3_prime_UTR_variant	16/16	1	NM_002103.5	P1	P13807-1
GYS1	ENST00000263276.6 linkuse as main transcript	c.*301G>A		3_prime_UTR_variant	15/15	1			P13807-2

Frequencies

GnomAD3 genomes

AF:

0.00185

AC:

282

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000555

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00662

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00703

Gnomad FIN

AF:

0.000941

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.00198

Gnomad OTH

AF:

0.00669

GnomAD3 exomes

AF:

0.00331

AC:

450

AN:

136062

Hom.:

AF XY:

0.00384

AC XY:

284

AN XY:

73928

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00222

Gnomad ASJ exome

AF:

0.00641

Gnomad EAS exome

AF:

0.0000959

Gnomad SAS exome

AF:

0.00957

Gnomad FIN exome

AF:

0.000186

Gnomad NFE exome

AF:

0.00181

Gnomad OTH exome

AF:

0.00654

GnomAD4 exome

AF:

0.00313

AC:

1437

AN:

459590

Hom.:

Cov.:

AF XY:

0.00366

AC XY:

919

AN XY:

250752

show subpopulations

Gnomad4 AFR exome

AF:

0.000654

Gnomad4 AMR exome

AF:

0.00190

Gnomad4 ASJ exome

AF:

0.00659

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00963

Gnomad4 FIN exome

AF:

0.000364

Gnomad4 NFE exome

AF:

0.00202

Gnomad4 OTH exome

AF:

0.00384

GnomAD4 genome

AF:

0.00185

AC:

282

AN:

152346

Hom.:

Cov.:

AF XY:

0.00196

AC XY:

146

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000553

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00662

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00704

Gnomad4 FIN

AF:

0.000941

Gnomad4 NFE

AF:

0.00198

Gnomad4 OTH

AF:

0.00662

Alfa

AF:

0.00240

Hom.:

Bravo

AF:

0.00182

Asia WGS

AF:

0.00404

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:2

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Glycogen storage disease due to muscle and heart glycogen synthase deficiency

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.93

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