15-42329603-C-T

Variant names:

• chr15-42329603-C-T
• rs4924673
• NM_198141.3:c.1644+154C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_198141.3(GANC):​c.1644+154C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0761 in 546,984 control chromosomes in the GnomAD database, including 2,329 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.10 (1142 hom., cov: 32)
  • Exomes 𝑓: 0.066 (1187 hom.)
• Consequence: GANC NM_198141.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.34

Genes affected

GANC (HGNC:4139): (glucosidase alpha, neutral C) Glycosyl hydrolase enzymes hydrolyse the glycosidic bond between two or more carbohydrates, or between a carbohydrate and a non-carbohydrate moiety. This gene encodes a member of glycosyl hydrolases family 31. This enzyme hydrolyses terminal, non-reducing 1,4-linked alpha-D-glucose residues and releases alpha-D-glucose. This is a key enzyme in glycogen metabolism and its gene localizes to a chromosomal region (15q15) that is associated with susceptibility to diabetes. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GANC	NM_198141.3	c.1644+154C>T		intron_variant	Intron 14 of 23	ENST00000318010.13	NP_937784.2
GANC	NM_001393928.1	c.1644+154C>T		intron_variant	Intron 15 of 24		NP_001380857.1
GANC	NM_001393929.1	c.1644+154C>T		intron_variant	Intron 15 of 24		NP_001380858.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GANC	ENST00000318010.13	c.1644+154C>T		intron_variant	Intron 14 of 23	1	NM_198141.3	ENSP00000326227.8
GANC	ENST00000568953.1	n.*99C>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15655 AN: 152010 Hom.: 1134 Cov.: 32

Gnomad AFR AF: 0.177

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.0554

Gnomad EAS AF: 0.103

Gnomad SAS AF: 0.0983

Gnomad FIN AF: 0.0303

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0533

Gnomad OTH AF: 0.107

GnomAD4 exome AF: 0.0657 AC: 25959 AN: 394856 Hom.: 1187 AF XY: 0.0664 AC XY: 13280 AN XY: 199962

Gnomad4 AFR exome AF: 0.173

Gnomad4 AMR exome AF: 0.246

Gnomad4 ASJ exome AF: 0.0516

Gnomad4 EAS exome AF: 0.0716

Gnomad4 SAS exome AF: 0.113

Gnomad4 FIN exome AF: 0.0322

Gnomad4 NFE exome AF: 0.0543

Gnomad4 OTH exome AF: 0.0814

GnomAD4 genome AF: 0.103 AC: 15680 AN: 152128 Hom.: 1142 Cov.: 32 AF XY: 0.104 AC XY: 7713 AN XY: 74390

Gnomad4 AFR AF: 0.177

Gnomad4 AMR AF: 0.193

Gnomad4 ASJ AF: 0.0554

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.0980

Gnomad4 FIN AF: 0.0303

Gnomad4 NFE AF: 0.0532

Gnomad4 OTH AF: 0.106

Alfa AF: 0.0221 Hom.: 4

Bravo AF: 0.119

Asia WGS AF: 0.115 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.15
DANN	Benign	0.72

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: rs4924673; hg19: chr15-42621801;