8-117173494-A-G

Position:

• chr8-117173494-A-G

Variant summary

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

The NM_173851.3(SLC30A8):​c.*813A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.254 in 152,070 control chromosomes in the GnomAD database, including 5,838 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 (5835 hom., cov: 33)
  • Exomes 𝑓: 0.26 (3 hom.)
• Consequence: SLC30A8 NM_173851.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A8	NM_173851.3	c.*813A>G		3_prime_UTR_variant	8/8	ENST00000456015.7
LOC105375716	XR_007061067.1	n.560-6T>C		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A8	ENST00000456015.7	c.*813A>G		3_prime_UTR_variant	8/8	1	NM_173851.3	P1
SLC30A8	ENST00000519688.5	c.*813A>G		3_prime_UTR_variant	9/9	1
SLC30A8	ENST00000427715.2	c.*813A>G		3_prime_UTR_variant	11/11	2

Frequencies

GnomAD3 genomes AF: 0.254 AC: 38550 AN: 151920 Hom.: 5832 Cov.: 33

Gnomad AFR AF: 0.0955

Gnomad AMI AF: 0.170

Gnomad AMR AF: 0.260

Gnomad ASJ AF: 0.278

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.235

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.261

GnomAD4 exome AF: 0.265 AC: 9 AN: 34 Hom.: 3 Cov.: 0 AF XY: 0.250 AC XY: 6 AN XY: 24

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.308

Gnomad4 OTH exome AF: 0.250

GnomAD4 genome AF: 0.254 AC: 38562 AN: 152036 Hom.: 5835 Cov.: 33 AF XY: 0.259 AC XY: 19208 AN XY: 74292

Gnomad4 AFR AF: 0.0954

Gnomad4 AMR AF: 0.260

Gnomad4 ASJ AF: 0.278

Gnomad4 EAS AF: 0.459

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.312

Gnomad4 OTH AF: 0.259

Alfa AF: 0.303 Hom.: 13161

Bravo AF: 0.241

Asia WGS AF: 0.299 AC: 1036 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	8.6
DANN	Benign	0.64

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: rs11558471; hg19: chr8-118185733;