8-117171312-G-C

Variant names:

• chr8-117171312-G-C
• rs2464592
• NM_173851.3:c.964+144G>C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000456015.7(SLC30A8):​c.964+144G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC30A8 ENST00000456015.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 10 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000456015.7. 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.964+144G>C		intron	N/A	NP_776250.2
	SLC30A8	NM_001172811.2		c.817+144G>C		intron	N/A	NP_001166282.1
	SLC30A8	NM_001172813.2		c.817+144G>C		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.964+144G>C		intron	N/A	ENSP00000415011.2
	SLC30A8	ENST00000519688.5	TSL:1	c.817+144G>C		intron	N/A	ENSP00000431069.1
	SLC30A8	ENST00000521243.5	TSL:1	c.817+144G>C		intron	N/A	ENSP00000428545.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 736308 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 386866

African (AFR) AF: 0.00 AC: 0 AN: 17812

American (AMR) AF: 0.00 AC: 0 AN: 33168

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17528

East Asian (EAS) AF: 0.00 AC: 0 AN: 34504

South Asian (SAS) AF: 0.00 AC: 0 AN: 59924

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 36550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2550

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 498522

Other (OTH) AF: 0.00 AC: 0 AN: 35750

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.3
DANN	Benign	0.60
PhyloP100		-0.0080

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: rs2464592; hg19: chr8-118183551;