Variant rs1042265 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_002103.5(GYS1):c.*725C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 454,382 control chromosomes in the GnomAD database, including 2,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.097 ( 763 hom., cov: 32)

Exomes 𝑓: 0.094 ( 1499 hom. )

Consequence

GYS1
NM_002103.5 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.153

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=-0.68).

BP6

Variant 19-48968563-G-A is Benign according to our data. Variant chr19-48968563-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 329796.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE	Protein
GYS1	NM_002103.5 linkuse as main transcript	c.*725C>T	3_prime_UTR_variant	16/16	ENST00000323798.8	NP_002094.2
GYS1	NM_001161587.2 linkuse as main transcript	c.*725C>T	3_prime_UTR_variant	15/15		NP_001155059.1
GYS1	NR_027763.2 linkuse as main transcript	n.2954C>T	non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GYS1	ENST00000323798.8 linkuse as main transcript	c.*725C>T		3_prime_UTR_variant	16/16	1	NM_002103.5	ENSP00000317904	P1	P13807-1
GYS1	ENST00000263276.6 linkuse as main transcript	c.*725C>T		3_prime_UTR_variant	15/15	1		ENSP00000263276		P13807-2

Frequencies

GnomAD3 genomes

AF:

0.0970

AC:

14754

AN:

152066

Hom.:

763

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0936

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.137

Gnomad ASJ

AF:

0.0839

Gnomad EAS

AF:

0.0507

Gnomad SAS

AF:

0.0573

Gnomad FIN

AF:

0.0610

Gnomad MID

AF:

0.0949

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.109

GnomAD3 exomes

AF:

0.0989

AC:

13477

AN:

136236

Hom.:

771

AF XY:

0.0933

AC XY:

6905

AN XY:

74030

show subpopulations

Gnomad AFR exome

AF:

0.0955

Gnomad AMR exome

AF:

0.162

Gnomad ASJ exome

AF:

0.0805

Gnomad EAS exome

AF:

0.0541

Gnomad SAS exome

AF:

0.0585

Gnomad FIN exome

AF:

0.0647

Gnomad NFE exome

AF:

0.103

Gnomad OTH exome

AF:

0.0886

GnomAD4 exome

AF:

0.0940

AC:

28417

AN:

302198

Hom.:

1499

Cov.:

AF XY:

0.0893

AC XY:

15384

AN XY:

172246

show subpopulations

Gnomad4 AFR exome

AF:

0.0984

Gnomad4 AMR exome

AF:

0.162

Gnomad4 ASJ exome

AF:

0.0810

Gnomad4 EAS exome

AF:

0.0514

Gnomad4 SAS exome

AF:

0.0578

Gnomad4 FIN exome

AF:

0.0622

Gnomad4 NFE exome

AF:

0.102

Gnomad4 OTH exome

AF:

0.0898

GnomAD4 genome

AF:

0.0970

AC:

14765

AN:

152184

Hom.:

763

Cov.:

AF XY:

0.0947

AC XY:

7044

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0938

Gnomad4 AMR

AF:

0.136

Gnomad4 ASJ

AF:

0.0839

Gnomad4 EAS

AF:

0.0504

Gnomad4 SAS

AF:

0.0577

Gnomad4 FIN

AF:

0.0610

Gnomad4 NFE

AF:

0.102

Gnomad4 OTH

AF:

0.109

Alfa

AF:

0.0922

Hom.:

546

Bravo

AF:

0.104

Asia WGS

AF:

0.0780

AC:

269

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -

Hereditary hyperferritinemia with congenital cataracts

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Neuroferritinopathy

Benign:1

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

9.9

DANN

Benign

0.79

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