Variant 19-48968447-T-C 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.*841A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0045 in 454,488 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 29 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 6 hom. )

Consequence

GYS1
NM_002103.5 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.200

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=-0.8).

BP6

Variant 19-48968447-T-C is Benign according to our data. Variant chr19-48968447-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 329794.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0107 (1622/152240) while in subpopulation AFR AF= 0.036 (1495/41542). AF 95% confidence interval is 0.0345. There are 29 homozygotes in gnomad4. There are 749 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
GYS1	NM_002103.5 linkuse as main transcript	c.*841A>G	3_prime_UTR_variant	16/16	ENST00000323798.8
GYS1	NM_001161587.2 linkuse as main transcript	c.*841A>G	3_prime_UTR_variant	15/15
GYS1	NR_027763.2 linkuse as main transcript	n.3070A>G	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.*841A>G		3_prime_UTR_variant	16/16	1	NM_002103.5	P1	P13807-1
GYS1	ENST00000263276.6 linkuse as main transcript	c.*841A>G		3_prime_UTR_variant	15/15	1			P13807-2

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1601

AN:

152122

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0356

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.00814

GnomAD3 exomes

AF:

0.00215

AC:

294

AN:

136594

Hom.:

AF XY:

0.00150

AC XY:

111

AN XY:

74178

show subpopulations

Gnomad AFR exome

AF:

0.0340

Gnomad AMR exome

AF:

0.00245

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000133

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000128

Gnomad OTH exome

AF:

0.00120

GnomAD4 exome

AF:

0.00140

AC:

424

AN:

302248

Hom.:

Cov.:

AF XY:

0.00104

AC XY:

180

AN XY:

172264

show subpopulations

Gnomad4 AFR exome

AF:

0.0344

Gnomad4 AMR exome

AF:

0.00224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000151

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000819

Gnomad4 OTH exome

AF:

0.00306

GnomAD4 genome

AF:

0.0107

AC:

1622

AN:

152240

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

749

AN XY:

74448

show subpopulations

Gnomad4 AFR

AF:

0.0360

Gnomad4 AMR

AF:

0.00602

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.00806

Alfa

AF:

0.00371

Hom.:

Bravo

AF:

0.0117

Asia WGS

AF:

0.00346

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

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 12, 2021

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

2.9

DANN

Benign

0.74

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