8-117146954-T-C

Variant names:

• chr8-117146954-T-C
• rs144023942
• ENST00000519688.5:c.-76T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_173851.3(SLC30A8):​c.72T>C​(p.Ser24Ser) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000568 in 1,613,828 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0030 (6 hom., cov: 32)
  • Exomes 𝑓: 0.00031 (4 hom.)
• Consequence: SLC30A8 NM_173851.3 splice_region, synonymous
• Scores: Splicing: ADA: 0.00003876
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.733
• Publications: 0 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 -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 8-117146954-T-C is Benign according to our data. Variant chr8-117146954-T-C is described in ClinVar as Benign. ClinVar VariationId is 791294.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.733 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 6 gene

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.72T>C	p.Ser24Ser	splice_region synonymous	Exon 2 of 8	NP_776250.2	Q8IWU4-1
	SLC30A8	NM_001172811.2		c.-76T>C		splice_region	Exon 4 of 10	NP_001166282.1	Q8IWU4-2
	SLC30A8	NM_001172813.2		c.-76T>C		splice_region	Exon 5 of 11	NP_001166284.1	Q8IWU4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC30A8	ENST00000519688.5	TSL:1	c.-76T>C		splice_region	Exon 3 of 9	ENSP00000431069.1	Q8IWU4-2
	SLC30A8	ENST00000521243.5	TSL:1	c.-76T>C		splice_region	Exon 4 of 10	ENSP00000428545.1	Q8IWU4-2
	SLC30A8	ENST00000456015.7	TSL:1 MANE Select	c.72T>C	p.Ser24Ser	splice_region synonymous	Exon 2 of 8	ENSP00000415011.2	Q8IWU4-1

Frequencies

GnomAD3 genomes AF: 0.00302 AC: 459 AN: 152104 Hom.: 6 Cov.: 32

Gnomad AFR AF: 0.0103

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00138

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00383

GnomAD2 exomes AF: 0.000808 AC: 203 AN: 251084 AF XY: 0.000553

Gnomad AFR exome AF: 0.0108

Gnomad AMR exome AF: 0.000667

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000490

GnomAD4 exome AF: 0.000313 AC: 457 AN: 1461608 Hom.: 4 Cov.: 31 AF XY: 0.000281 AC XY: 204 AN XY: 727102

African (AFR) AF: 0.0107 AC: 358 AN: 33468

American (AMR) AF: 0.000627 AC: 28 AN: 44658

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39692

South Asian (SAS) AF: 0.000139 AC: 12 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53410

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5760

European-Non Finnish (NFE) AF: 0.00000270 AC: 3 AN: 1111866

Other (OTH) AF: 0.000894 AC: 54 AN: 60378

GnomAD4 genome AF: 0.00302 AC: 460 AN: 152220 Hom.: 6 Cov.: 32 AF XY: 0.00300 AC XY: 223 AN XY: 74432

African (AFR) AF: 0.0103 AC: 428 AN: 41552

American (AMR) AF: 0.00137 AC: 21 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 68008

Other (OTH) AF: 0.00379 AC: 8 AN: 2112

Alfa AF: 0.00114 Hom.: 4

Bravo AF: 0.00341

Asia WGS AF: 0.000866 AC: 3 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.8
DANN	Benign	0.53
PhyloP100		-0.73
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000039
dbscSNV1_RF	Benign	0.040
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: rs144023942; hg19: chr8-118159193;