rs3802177

chr8-117172786-G-A

Variant summary

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

The NM_173851.3(SLC30A8):c.*105G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 1,327,950 control chromosomes in the GnomAD database, including 59,489 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 0.25 (5605 hom., cov: 33)
  • Exomes 𝑓: 0.30 (53884 hom.)
• Consequence: SLC30A8 NM_173851.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44

Genes affected

SLC30A8 (HGNC:20303): (solute carrier family 30 member 8) The protein encoded by this gene is a zinc efflux transporter involved in the accumulation of zinc in intracellular vesicles. This gene is expressed at a high level only in the pancreas, particularly in islets of Langerhans. The encoded protein colocalizes with insulin in the secretory pathway granules of the insulin-secreting INS-1 cells. Allelic variants of this gene exist that confer susceptibility to diabetes mellitus, noninsulin-dependent (NIDDM). Several transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Mar 2010]

LOC105375716 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A8	NM_173851.3	c.*105G>A		3_prime_UTR_variant	8/8	ENST00000456015.7
LOC105375716	XR_007061067.1	n.689-41C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A8	ENST00000456015.7	c.*105G>A		3_prime_UTR_variant	8/8	1	NM_173851.3	P1
SLC30A8	ENST00000519688.5	c.*105G>A		3_prime_UTR_variant	9/9	1
SLC30A8	ENST00000521243.5	c.*105G>A		3_prime_UTR_variant	10/10	1
SLC30A8	ENST00000427715.2	c.*105G>A		3_prime_UTR_variant	11/11	2

Frequencies

GnomAD3 genomes AF: 0.249 AC: 37793 AN: 151974 Hom.: 5603 Cov.: 33

Gnomad AFR AF: 0.0942

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.456

Gnomad SAS AF: 0.232

Gnomad FIN AF: 0.399

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.305

Gnomad OTH AF: 0.255

GnomAD4 exome AF: 0.296 AC: 347970 AN: 1175858 Hom.: 53884 Cov.: 16 AF XY: 0.295 AC XY: 174482 AN XY: 591392

Gnomad4 AFR exome AF: 0.0799

Gnomad4 AMR exome AF: 0.248

Gnomad4 ASJ exome AF: 0.264

Gnomad4 EAS exome AF: 0.437

Gnomad4 SAS exome AF: 0.230

Gnomad4 FIN exome AF: 0.377

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.286

GnomAD4 genome AF: 0.249 AC: 37807 AN: 152092 Hom.: 5605 Cov.: 33 AF XY: 0.253 AC XY: 18845 AN XY: 74344

Gnomad4 AFR AF: 0.0941

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.269

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.232

Gnomad4 FIN AF: 0.399

Gnomad4 NFE AF: 0.305

Gnomad4 OTH AF: 0.253

Alfa AF: 0.294 Hom.: 7582

Bravo AF: 0.235

Asia WGS AF: 0.292 AC: 1012 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	2.8
Dann	Benign	0.28

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: rs3802177; hg19: chr8-118185025; COSMIC: COSV69968186;