Variant 19-48968171-ACACT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6BS1BS2

The NM_002103.5(GYS1):c.*1113_*1116del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00295 in 453,768 control chromosomes in the GnomAD database, including 12 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.0070 ( 8 hom., cov: 32)

Exomes 𝑓: 0.00091 ( 4 hom. )

Consequence

GYS1
NM_002103.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:3

Conservation

PhyloP100: 1.61

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 -9 ACMG points.

BP6

Variant 19-48968171-ACACT-A is Benign according to our data. Variant chr19-48968171-ACACT-A is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 329790.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=3, Uncertain_significance=1}.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00699 (1064/152260) while in subpopulation AFR AF= 0.0245 (1018/41556). AF 95% confidence interval is 0.0232. There are 8 homozygotes in gnomad4. There are 490 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
GYS1	NM_002103.5 linkuse as main transcript	c.1113_1116del	3_prime_UTR_variant	16/16	ENST00000323798.8
GYS1	NM_001161587.2 linkuse as main transcript	c.1113_1116del	3_prime_UTR_variant	15/15
GYS1	NR_027763.2 linkuse as main transcript	n.3342_3345del	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.1113_1116del		3_prime_UTR_variant	16/16	1	NM_002103.5	P1	P13807-1
GYS1	ENST00000263276.6 linkuse as main transcript	c.1113_1116del		3_prime_UTR_variant	15/15	1			P13807-2

Frequencies

GnomAD3 genomes

AF:

0.00701

AC:

1067

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0246

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00144

AC:

190

AN:

132320

Hom.:

AF XY:

0.00115

AC XY:

AN XY:

72198

show subpopulations

Gnomad AFR exome

AF:

0.0266

Gnomad AMR exome

AF:

0.00103

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000447

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000247

GnomAD4 exome

AF:

0.000905

AC:

273

AN:

301508

Hom.:

AF XY:

0.000634

AC XY:

109

AN XY:

171790

show subpopulations

Gnomad4 AFR exome

AF:

0.0265

Gnomad4 AMR exome

AF:

0.00103

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000503

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000631

Gnomad4 OTH exome

AF:

0.000998

GnomAD4 genome

AF:

0.00699

AC:

1064

AN:

152260

Hom.:

Cov.:

AF XY:

0.00658

AC XY:

490

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0245

Gnomad4 AMR

AF:

0.00216

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00365

Hom.:

Bravo

AF:

0.00788

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:3

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

- -

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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