rs1042265

Positions:

• chr19-48968563-G-A
• chr19-48968563-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.153

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]

ACMG classification

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	HGVSp	Effect	#exon/exons	MANE	UniProt
GYS1	NM_002103.5	c.*725C>T		3_prime_UTR_variant	16/16	ENST00000323798.8
GYS1	NM_001161587.2	c.*725C>T		3_prime_UTR_variant	15/15
GYS1	NR_027763.2	n.2954C>T		non_coding_transcript_exon_variant	15/15

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GYS1	ENST00000323798.8	c.*725C>T		3_prime_UTR_variant	16/16	1	NM_002103.5	P1
GYS1	ENST00000263276.6	c.*725C>T		3_prime_UTR_variant	15/15	1

Frequencies

GnomAD3 genomes AF: 0.0970 AC: 14754 AN: 152066 Hom.: 763 Cov.: 32

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

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.: 0 AF XY: 0.0893 AC XY: 15384 AN XY: 172246

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.: 32 AF XY: 0.0947 AC XY: 7044 AN XY: 74392

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

not provided Benign:1

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	-0.68
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

Other links and lift over

dbSNP: rs1042265; hg19: chr19-49471820;