8-117171039-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_173851.3(SLC30A8):c.835C>T(p.Pro279Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SLC30A8 NM_173851.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.35

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

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC30A8	NM_173851.3	c.835C>T	p.Pro279Ser	missense_variant	7/8	ENST00000456015.7
LOC105375716	XR_007061067.1	n.819+1576G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC30A8	ENST00000456015.7	c.835C>T	p.Pro279Ser	missense_variant	7/8	1	NM_173851.3	P1
SLC30A8	ENST00000519688.5	c.688C>T	p.Pro230Ser	missense_variant	8/9	1
SLC30A8	ENST00000521243.5	c.688C>T	p.Pro230Ser	missense_variant	9/10	1
SLC30A8	ENST00000427715.2	c.688C>T	p.Pro230Ser	missense_variant	10/11	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 13, 2021

The c.835C>T (p.P279S) alteration is located in exon 7 (coding exon 7) of the SLC30A8 gene. This alteration results from a C to T substitution at nucleotide position 835, causing the proline (P) at amino acid position 279 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
Cadd	Benign	23
Dann	Pathogenic	1.0
Eigen	Uncertain	0.67
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.057	D
MetaRNN	Uncertain	0.74	D;D;D;D
MetaSVM	Uncertain	0.075	D
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Pathogenic	-7.4	D;D;D;D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.014	D;D;D;D
Sift4G	Uncertain	0.014	D;D;D;D
Polyphen		1.0	.;.;.;D
Vest4		0.26
MutPred		0.83		.;.;.;Gain of disorder (P = 0.0643);
MVP		0.76
MPC		0.16
ClinPred		1.0	D
GERP RS		3.2
Varity_R		0.64
gMVP		0.84

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

Publications

LitVar

Other links and lift over

dbSNP: rs1360609984; hg19: chr8-118183278;