rs6469675

Variant names:

• chr8-117152910-A-G
• rs6469675
• NM_173851.3:c.272-34A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_173851.3(SLC30A8):​c.272-34A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 1,456,850 control chromosomes in the GnomAD database, including 71,357 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 0.39 (14256 hom., cov: 32)
  • Exomes 𝑓: 0.29 (57101 hom.)
• Consequence: SLC30A8 NM_173851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.645
• Publications: 12 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.688 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_173851.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A8	NM_173851.3	MANE Select	c.272-34A>G		intron	N/A	NP_776250.2
	SLC30A8	NM_001172811.2		c.125-34A>G		intron	N/A	NP_001166282.1
	SLC30A8	NM_001172813.2		c.125-34A>G		intron	N/A	NP_001166284.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A8	ENST00000456015.7	TSL:1 MANE Select	c.272-34A>G		intron	N/A	ENSP00000415011.2
	SLC30A8	ENST00000519688.5	TSL:1	c.125-34A>G		intron	N/A	ENSP00000431069.1
	SLC30A8	ENST00000521243.5	TSL:1	c.125-34A>G		intron	N/A	ENSP00000428545.1

Frequencies

GnomAD3 genomes AF: 0.385 AC: 58440 AN: 151820 Hom.: 14211 Cov.: 32

Gnomad AFR AF: 0.695

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.283

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.282

Gnomad FIN AF: 0.203

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.346

GnomAD2 exomes AF: 0.305 AC: 61828 AN: 202860 AF XY: 0.297

Gnomad AFR exome AF: 0.705

Gnomad AMR exome AF: 0.226

Gnomad ASJ exome AF: 0.271

Gnomad EAS exome AF: 0.380

Gnomad FIN exome AF: 0.215

Gnomad NFE exome AF: 0.274

Gnomad OTH exome AF: 0.289

GnomAD4 exome AF: 0.285 AC: 371939 AN: 1304912 Hom.: 57101 Cov.: 28 AF XY: 0.284 AC XY: 180956 AN XY: 637736

African (AFR) AF: 0.709 AC: 21704 AN: 30626

American (AMR) AF: 0.233 AC: 8124 AN: 34892

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 5502 AN: 20538

East Asian (EAS) AF: 0.333 AC: 12219 AN: 36748

South Asian (SAS) AF: 0.281 AC: 16558 AN: 58954

European-Finnish (FIN) AF: 0.221 AC: 10448 AN: 47322

Middle Eastern (MID) AF: 0.280 AC: 1438 AN: 5128

European-Non Finnish (NFE) AF: 0.275 AC: 279797 AN: 1017584

Other (OTH) AF: 0.304 AC: 16149 AN: 53120

GnomAD4 genome AF: 0.385 AC: 58545 AN: 151938 Hom.: 14256 Cov.: 32 AF XY: 0.378 AC XY: 28093 AN XY: 74248

African (AFR) AF: 0.695 AC: 28785 AN: 41404

American (AMR) AF: 0.283 AC: 4321 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 918 AN: 3468

East Asian (EAS) AF: 0.351 AC: 1809 AN: 5148

South Asian (SAS) AF: 0.282 AC: 1348 AN: 4782

European-Finnish (FIN) AF: 0.203 AC: 2146 AN: 10594

Middle Eastern (MID) AF: 0.286 AC: 84 AN: 294

European-Non Finnish (NFE) AF: 0.268 AC: 18195 AN: 67944

Other (OTH) AF: 0.346 AC: 731 AN: 2110

Alfa AF: 0.287 Hom.: 7126

Bravo AF: 0.404

Asia WGS AF: 0.368 AC: 1281 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.63
DANN	Benign	0.84
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6469675; hg19: chr8-118165149; COSMIC: COSV69975167;