chr4-42063005-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_006345.4(SLC30A9):c.916C>T(p.Arg306Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,611,852 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000031 ( 0 hom. )
Consequence
SLC30A9
NM_006345.4 missense
NM_006345.4 missense
Scores
13
4
2
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
SLC30A9 (HGNC:1329): (solute carrier family 30 member 9) Predicted to enable nuclear receptor coactivator activity. Involved in cellular zinc ion homeostasis and zinc ion transport. Located in several cellular components, including cytoplasmic vesicle; cytoskeleton; and endoplasmic reticulum. [provided by Alliance of Genome Resources, Apr 2022]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.913
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC30A9 | NM_006345.4 | c.916C>T | p.Arg306Cys | missense_variant | 11/18 | ENST00000264451.12 | |
SLC30A9 | XM_047449525.1 | c.916C>T | p.Arg306Cys | missense_variant | 11/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC30A9 | ENST00000264451.12 | c.916C>T | p.Arg306Cys | missense_variant | 11/18 | 1 | NM_006345.4 | P1 | |
SLC30A9 | ENST00000513699.5 | c.*673C>T | 3_prime_UTR_variant, NMD_transcript_variant | 12/19 | 2 | ||||
SLC30A9 | ENST00000509683.5 | upstream_gene_variant | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152046Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250558Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135380
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GnomAD4 exome AF: 0.0000308 AC: 45AN: 1459806Hom.: 0 Cov.: 29 AF XY: 0.0000262 AC XY: 19AN XY: 726254
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GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152046Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74230
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 07, 2021 | The c.916C>T (p.R306C) alteration is located in exon 11 (coding exon 11) of the SLC30A9 gene. This alteration results from a C to T substitution at nucleotide position 916, causing the arginine (R) at amino acid position 306 to be replaced by a cysteine (C). 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
Pathogenic
Dann
Pathogenic
DEOGEN2
Benign
T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D
MetaSVM
Uncertain
D
MutationAssessor
Pathogenic
H
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Pathogenic
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
D
Vest4
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
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