chr8-117171039-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
NM_173851.3 missense
Scores
5
8
3
Clinical Significance
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]
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ACMG classification
Classification made for transcript
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
GnomAD3 genomes
?
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
Cadd
Benign
Dann
Pathogenic
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0
.;.;.;D
Vest4
MutPred
0.83
.;.;.;Gain of disorder (P = 0.0643);
MVP
MPC
0.16
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at