rs10282940

Variant names:

• chr8-117175587-G-A
• rs10282940
• NM_173851.3:c.*2906G>A

Variant summary

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

The NM_173851.3(SLC30A8):​c.*2906G>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 0.133 in 152,108 control chromosomes in the GnomAD database, including 1,654 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 0.13 (1654 hom., cov: 33)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: SLC30A8 NM_173851.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.12
• Publications: 13 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]

SLC30A8 Gene-Disease associations (from GenCC):

• type 2 diabetes mellitus

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

LOC105375716 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.231 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A8	NM_173851.3	MANE Select	c.*2906G>A		3_prime_UTR	Exon 8 of 8	NP_776250.2	Q8IWU4-1
	SLC30A8	NM_001172811.2		c.*2906G>A		3_prime_UTR	Exon 10 of 10	NP_001166282.1	Q8IWU4-2
	SLC30A8	NM_001172813.2		c.*2906G>A		3_prime_UTR	Exon 11 of 11	NP_001166284.1	Q8IWU4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A8	ENST00000456015.7	TSL:1 MANE Select	c.*2906G>A		3_prime_UTR	Exon 8 of 8	ENSP00000415011.2	Q8IWU4-1
	SLC30A8	ENST00000519688.5	TSL:1	c.*2906G>A		3_prime_UTR	Exon 9 of 9	ENSP00000431069.1	Q8IWU4-2
	SLC30A8	ENST00000427715.2	TSL:2	c.*2906G>A		3_prime_UTR	Exon 11 of 11	ENSP00000407505.2	Q8IWU4-2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20246 AN: 151986 Hom.: 1654 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.120

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0104

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.0504

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0988

Gnomad OTH AF: 0.130

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.133 AC: 20248 AN: 152104 Hom.: 1654 Cov.: 33 AF XY: 0.130 AC XY: 9645 AN XY: 74366

African (AFR) AF: 0.235 AC: 9753 AN: 41472

American (AMR) AF: 0.120 AC: 1831 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3468

East Asian (EAS) AF: 0.0105 AC: 54 AN: 5162

South Asian (SAS) AF: 0.127 AC: 613 AN: 4824

European-Finnish (FIN) AF: 0.0504 AC: 535 AN: 10612

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0988 AC: 6715 AN: 67988

Other (OTH) AF: 0.129 AC: 272 AN: 2114

Alfa AF: 0.109 Hom.: 4503

Bravo AF: 0.142

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.7
DANN	Benign	0.49
PhyloP100		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs10282940; hg19: chr8-118187826;