2-32193953-C-T

Variant summary

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

The NM_001330477.2(SLC30A6):​c.-152C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000415 in 1,613,090 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000040 ( 0 hom. )

Consequence

SLC30A6
NM_001330477.2 5_prime_UTR_premature_start_codon_gain

Scores

3
11
5

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31
Variant links:
Genes affected
SLC30A6 (HGNC:19305): (solute carrier family 30 member 6) This gene encodes a member of a family of proteins that function as zinc transporters. This protein can regulate subcellular levels of zinc in the Golgi and vesicles. Expression of this gene is altered in the Alzheimer's disease brain plaques. [provided by RefSeq, Aug 2016]

Genome browser will be placed here

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 rank MANE Protein UniProt
SLC30A6NM_017964.5 linkc.466C>T p.Arg156Trp missense_variant Exon 8 of 14 ENST00000282587.9 NP_060434.2 Q6NXT4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC30A6ENST00000282587.9 linkc.466C>T p.Arg156Trp missense_variant Exon 8 of 14 1 NM_017964.5 ENSP00000282587.5 Q6NXT4-1

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152052
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000735
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.0000638
AC:
16
AN:
250930
Hom.:
0
AF XY:
0.0000885
AC XY:
12
AN XY:
135632
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000290
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000164
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000397
AC:
58
AN:
1460920
Hom.:
0
Cov.:
30
AF XY:
0.0000509
AC XY:
37
AN XY:
726772
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000387
Gnomad4 OTH exome
AF:
0.0000663
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152170
Hom.:
0
Cov.:
33
AF XY:
0.0000806
AC XY:
6
AN XY:
74402
show subpopulations
Gnomad4 AFR
AF:
0.0000482
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000735
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.0000450
Hom.:
0
Bravo
AF:
0.0000378
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000659
AC:
8
EpiCase
AF:
0.0000546
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 13, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.586C>T (p.R196W) alteration is located in exon 9 (coding exon 9) of the SLC30A6 gene. This alteration results from a C to T substitution at nucleotide position 586, causing the arginine (R) at amino acid position 196 to be replaced by a tryptophan (W). 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
Benign
0.26
BayesDel_addAF
Uncertain
0.14
D
BayesDel_noAF
Pathogenic
0.22
CADD
Pathogenic
29
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.087
.;.;T;.;T;T
Eigen
Uncertain
0.55
Eigen_PC
Uncertain
0.57
FATHMM_MKL
Uncertain
0.81
D
LIST_S2
Pathogenic
0.99
D;D;D;D;D;D
M_CAP
Benign
0.050
D
MetaRNN
Uncertain
0.50
D;D;D;D;D;D
MetaSVM
Benign
-0.37
T
MutationAssessor
Uncertain
2.3
.;M;.;.;M;.
PrimateAI
Uncertain
0.64
T
PROVEAN
Uncertain
-3.8
.;D;D;D;D;D
REVEL
Uncertain
0.55
Sift
Uncertain
0.0030
.;D;D;D;D;D
Sift4G
Uncertain
0.010
D;D;D;D;D;D
Polyphen
0.99, 1.0, 0.99
.;D;.;D;D;.
Vest4
0.60
MVP
0.60
MPC
0.20
ClinPred
0.79
D
GERP RS
4.8
Varity_R
0.40
gMVP
0.75

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs148435831; hg19: chr2-32419022; COSMIC: COSV50873583; COSMIC: COSV50873583; API