chr1-26045009-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP5BS2_Supporting

The NM_001004434.3(SLC30A2):​c.259G>A​(p.Gly87Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,614,152 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (no stars).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)
Exomes 𝑓: 0.000021 ( 0 hom. )

Consequence

SLC30A2
NM_001004434.3 missense

Scores

7
8
4

Clinical Significance

Pathogenic no assertion criteria provided P:1

Conservation

PhyloP100: 7.69
Variant links:
Genes affected
SLC30A2 (HGNC:11013): (solute carrier family 30 member 2) The protein encoded by this gene is a zinc transporter that acts as a homodimer. The encoded protein plays a role in secreting zinc into breast milk. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PP5
Variant 1-26045009-C-T is Pathogenic according to our data. Variant chr1-26045009-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 39553.Status of the report is no_assertion_criteria_provided, 0 stars.
BS2
High AC in GnomAd4 at 6 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC30A2NM_001004434.3 linkc.259G>A p.Gly87Arg missense_variant Exon 2 of 8 ENST00000374276.4 NP_001004434.1 Q9BRI3-2
SLC30A2NM_032513.5 linkc.259G>A p.Gly87Arg missense_variant Exon 2 of 7 NP_115902.1 Q9BRI3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC30A2ENST00000374276.4 linkc.259G>A p.Gly87Arg missense_variant Exon 2 of 8 1 NM_001004434.3 ENSP00000363394.3 Q9BRI3-2
SLC30A2ENST00000374278.7 linkc.259G>A p.Gly87Arg missense_variant Exon 2 of 7 1 ENSP00000363396.3 Q9BRI3-1
SLC30A2ENST00000498060.1 linkn.443G>A non_coding_transcript_exon_variant Exon 1 of 3 5

Frequencies

GnomAD3 genomes
AF:
0.0000394
AC:
6
AN:
152216
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000288
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000282
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000557
AC:
14
AN:
251450
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000893
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000139
Gnomad NFE exome
AF:
0.00000879
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000212
AC:
31
AN:
1461818
Hom.:
0
Cov.:
32
AF XY:
0.0000193
AC XY:
14
AN XY:
727218
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.000689
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.0000936
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000394
AC:
6
AN:
152334
Hom.:
0
Cov.:
33
AF XY:
0.0000671
AC XY:
5
AN XY:
74486
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000288
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000282
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000125
Hom.:
0
Bravo
AF:
0.0000264
ExAC
AF:
0.0000412
AC:
5
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link

Submissions by phenotype

Zinc deficiency, transient neonatal Pathogenic:1
Aug 24, 2012
OMIM
Significance: Pathogenic
Review Status: no assertion criteria provided
Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.90
BayesDel_addAF
Pathogenic
0.18
D
BayesDel_noAF
Pathogenic
0.21
CADD
Pathogenic
33
DANN
Pathogenic
1.0
DEOGEN2
Uncertain
0.53
D;.
Eigen
Uncertain
0.49
Eigen_PC
Uncertain
0.55
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.89
D;D
M_CAP
Benign
0.074
D
MetaRNN
Uncertain
0.74
D;D
MetaSVM
Benign
-0.41
T
MutationAssessor
Benign
1.5
L;L
PrimateAI
Uncertain
0.64
T
PROVEAN
Pathogenic
-5.7
D;D
REVEL
Pathogenic
0.80
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0030
D;D
Polyphen
1.0
D;P
Vest4
0.84
MutPred
0.76
Loss of catalytic residue at I86 (P = 0.2214);Loss of catalytic residue at I86 (P = 0.2214);
MVP
0.65
MPC
1.1
ClinPred
0.79
D
GERP RS
5.9
Varity_R
0.78
gMVP
0.95

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.10
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: rs185398527; hg19: chr1-26371500; COSMIC: COSV65332522; COSMIC: COSV65332522; API