8-117110827-C-G

Variant names:

• chr8-117110827-C-G
• rs13269119
• ENST00000521243.5:c.-106-35992C>G

Variant summary

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

The NM_001172811.2(SLC30A8):​c.-106-35992C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 152,074 control chromosomes in the GnomAD database, including 1,246 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 0.11 (1246 hom., cov: 32)
• Consequence: SLC30A8 NM_001172811.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.318
• Publications: 3 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001172811.2. 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_001172811.2		c.-106-35992C>G		intron	N/A	NP_001166282.1	Q8IWU4-2
	SLC30A8	NM_001172813.2		c.-273-24405C>G		intron	N/A	NP_001166284.1	Q8IWU4-2
	SLC30A8	NM_001172815.3		c.-225-24453C>G		intron	N/A	NP_001166286.1	Q8IWU4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A8	ENST00000521243.5	TSL:1	c.-106-35992C>G		intron	N/A	ENSP00000428545.1	Q8IWU4-2
	SLC30A8	ENST00000427715.2	TSL:2	c.-225-24453C>G		intron	N/A	ENSP00000407505.2	Q8IWU4-2
	SLC30A8	ENST00000524274.5	TSL:4	c.-106-35992C>G		intron	N/A	ENSP00000427760.1	E5RG87

Frequencies

GnomAD3 genomes AF: 0.113 AC: 17233 AN: 151958 Hom.: 1246 Cov.: 32

Gnomad AFR AF: 0.0349

Gnomad AMI AF: 0.125

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.141

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.0332

Gnomad FIN AF: 0.149

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.104

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.113 AC: 17249 AN: 152074 Hom.: 1246 Cov.: 32 AF XY: 0.111 AC XY: 8215 AN XY: 74322

African (AFR) AF: 0.0352 AC: 1459 AN: 41502

American (AMR) AF: 0.108 AC: 1653 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.141 AC: 489 AN: 3470

East Asian (EAS) AF: 0.146 AC: 754 AN: 5162

South Asian (SAS) AF: 0.0339 AC: 163 AN: 4810

European-Finnish (FIN) AF: 0.149 AC: 1579 AN: 10566

Middle Eastern (MID) AF: 0.103 AC: 30 AN: 292

European-Non Finnish (NFE) AF: 0.159 AC: 10790 AN: 67974

Other (OTH) AF: 0.103 AC: 218 AN: 2110

Alfa AF: 0.129 Hom.: 165

Bravo AF: 0.107

Asia WGS AF: 0.0700 AC: 244 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.9
DANN	Benign	0.37
PhyloP100		0.32
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: rs13269119; hg19: chr8-118123066;