chr8-117161811-G-A
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Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_173851.3(SLC30A8):c.646G>A(p.Ala216Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000159 in 1,613,868 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
SLC30A8
NM_173851.3 missense
NM_173851.3 missense
Scores
7
6
3
Clinical Significance
Conservation
PhyloP100: 5.75
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.646G>A | p.Ala216Thr | missense_variant | 5/8 | ENST00000456015.7 | |
LOC105375716 | XR_007061067.1 | n.819+10804C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC30A8 | ENST00000456015.7 | c.646G>A | p.Ala216Thr | missense_variant | 5/8 | 1 | NM_173851.3 | P1 | |
SLC30A8 | ENST00000519688.5 | c.499G>A | p.Ala167Thr | missense_variant | 6/9 | 1 | |||
SLC30A8 | ENST00000521243.5 | c.499G>A | p.Ala167Thr | missense_variant | 7/10 | 1 | |||
SLC30A8 | ENST00000427715.2 | c.499G>A | p.Ala167Thr | missense_variant | 8/11 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000986 AC: 15AN: 152148Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000637 AC: 16AN: 251164Hom.: 0 AF XY: 0.0000589 AC XY: 8AN XY: 135736
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GnomAD4 exome AF: 0.000165 AC: 241AN: 1461720Hom.: 0 Cov.: 30 AF XY: 0.000180 AC XY: 131AN XY: 727158
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GnomAD4 genome AF: 0.0000986 AC: 15AN: 152148Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8AN XY: 74322
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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 | Dec 07, 2021 | The c.646G>A (p.A216T) alteration is located in exon 5 (coding exon 5) of the SLC30A8 gene. This alteration results from a G to A substitution at nucleotide position 646, causing the alanine (A) at amino acid position 216 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Uncertain
DANN
Pathogenic
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
D
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D
REVEL
Pathogenic
Sift
Pathogenic
D;D;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0
.;.;.;D
Vest4
MVP
MPC
0.32
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at