chr8-117153064-G-T

Variant names:

• chr8-117153064-G-T
• rs778716564
• NM_173851.3:c.392G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_173851.3(SLC30A8):​c.392G>T​(p.Arg131Leu) variant causes a missense 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R131Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC30A8 NM_173851.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.23796159).

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.392G>T	p.Arg131Leu	missense	Exon 3 of 8	NP_776250.2	Q8IWU4-1
	SLC30A8	NM_001172811.2		c.245G>T	p.Arg82Leu	missense	Exon 5 of 10	NP_001166282.1	Q8IWU4-2
	SLC30A8	NM_001172813.2		c.245G>T	p.Arg82Leu	missense	Exon 6 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.392G>T	p.Arg131Leu	missense	Exon 3 of 8	ENSP00000415011.2	Q8IWU4-1
	SLC30A8	ENST00000519688.5	TSL:1	c.245G>T	p.Arg82Leu	missense	Exon 4 of 9	ENSP00000431069.1	Q8IWU4-2
	SLC30A8	ENST00000521243.5	TSL:1	c.245G>T	p.Arg82Leu	missense	Exon 5 of 10	ENSP00000428545.1	Q8IWU4-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.087	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Benign	0.086	T
Eigen	Benign	-0.99
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.082	N
LIST_S2	Uncertain	0.89	D
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.63	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		-0.25
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.26
Sift	Benign	0.14	T
Sift4G	Uncertain	0.039	D
Polyphen		0.34	B
Vest4		0.48
MutPred		0.68		Loss of disorder (P = 0.0332)
MVP		0.27
MPC		0.21
ClinPred		0.58	D
GERP RS		-5.3
Varity_R		0.30
gMVP		0.34
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs778716564; hg19: chr8-118165303;