rs924922

Variant names:

• chr8-117157479-G-A
• rs924922
• NM_173851.3:c.419-212G>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.419-212G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 152,092 control chromosomes in the GnomAD database, including 14,142 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 0.38 (14142 hom., cov: 32)
• Consequence: SLC30A8 NM_173851.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.44
• Publications: 2 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=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.687 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.419-212G>A		intron	N/A	NP_776250.2
	SLC30A8	NM_001172811.2		c.272-212G>A		intron	N/A	NP_001166282.1
	SLC30A8	NM_001172813.2		c.272-212G>A		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.419-212G>A		intron	N/A	ENSP00000415011.2
	SLC30A8	ENST00000519688.5	TSL:1	c.272-212G>A		intron	N/A	ENSP00000431069.1
	SLC30A8	ENST00000521243.5	TSL:1	c.272-212G>A		intron	N/A	ENSP00000428545.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58087 AN: 151974 Hom.: 14097 Cov.: 32

Gnomad AFR AF: 0.693

Gnomad AMI AF: 0.229

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.275

Gnomad NFE AF: 0.265

Gnomad OTH AF: 0.341

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

GnomAD4 genome AF: 0.383 AC: 58192 AN: 152092 Hom.: 14142 Cov.: 32 AF XY: 0.376 AC XY: 27937 AN XY: 74346

African (AFR) AF: 0.694 AC: 28769 AN: 41472

American (AMR) AF: 0.278 AC: 4247 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 905 AN: 3470

East Asian (EAS) AF: 0.347 AC: 1794 AN: 5168

South Asian (SAS) AF: 0.280 AC: 1352 AN: 4826

European-Finnish (FIN) AF: 0.199 AC: 2105 AN: 10586

Middle Eastern (MID) AF: 0.289 AC: 85 AN: 294

European-Non Finnish (NFE) AF: 0.265 AC: 18007 AN: 67974

Other (OTH) AF: 0.340 AC: 719 AN: 2112

Alfa AF: 0.332 Hom.: 1342

Bravo AF: 0.401

Asia WGS AF: 0.361 AC: 1256 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	10
DANN	Benign	0.37
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs924922; hg19: chr8-118169718; COSMIC: COSV69974034; COSMIC: COSV69974034;