1-100912233-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_133496.5(SLC30A7):​c.506G>T​(p.Gly169Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,372 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G169D) has been classified as Benign.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

SLC30A7
NM_133496.5 missense

Scores

7
9
3

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.57

Publications

0 publications found
Variant links:
Genes affected
SLC30A7 (HGNC:19306): (solute carrier family 30 member 7) Zinc functions as a cofactor for numerous enzymes, nuclear factors, and hormones and as an intra- and intercellular signal ion. Members of the zinc transporter (ZNT)/SLC30 subfamily of the cation diffusion facilitator family, such as SLC30A7, permit cellular efflux of zinc (Seve et al., 2004 [PubMed 15154973]).[supplied by OMIM, Mar 2008]
SLC30A7 Gene-Disease associations (from GenCC):
  • Joubert syndrome
    Inheritance: AD Classification: LIMITED Submitted by: G2P

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.842

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC30A7NM_133496.5 linkc.506G>T p.Gly169Val missense_variant Exon 5 of 11 ENST00000357650.9 NP_598003.2 Q8NEW0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC30A7ENST00000357650.9 linkc.506G>T p.Gly169Val missense_variant Exon 5 of 11 1 NM_133496.5 ENSP00000350278.4 Q8NEW0
SLC30A7ENST00000370112.8 linkc.506G>T p.Gly169Val missense_variant Exon 5 of 12 1 ENSP00000359130.4 Q8NEW0
SLC30A7ENST00000850622.1 linkn.506G>T non_coding_transcript_exon_variant Exon 5 of 13 ENSP00000520907.1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461372
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
726984
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33458
American (AMR)
AF:
0.00
AC:
0
AN:
44676
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26126
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39658
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86126
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53406
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5764
European-Non Finnish (NFE)
AF:
8.99e-7
AC:
1
AN:
1111786
Other (OTH)
AF:
0.00
AC:
0
AN:
60372
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.575
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.20
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.13
CADD
Pathogenic
29
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.63
D;D
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.74
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.92
.;D
M_CAP
Uncertain
0.090
D
MetaRNN
Pathogenic
0.84
D;D
MetaSVM
Uncertain
0.090
D
MutationAssessor
Pathogenic
3.6
H;H
PhyloP100
3.6
PrimateAI
Benign
0.39
T
PROVEAN
Pathogenic
-6.2
D;D
REVEL
Uncertain
0.55
Sift
Uncertain
0.0090
D;D
Sift4G
Uncertain
0.0070
D;D
Polyphen
1.0
D;D
Vest4
0.68
MutPred
0.56
Loss of phosphorylation at S170 (P = 0.1799);Loss of phosphorylation at S170 (P = 0.1799);
MVP
0.82
MPC
0.46
ClinPred
0.99
D
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.90
gMVP
0.64
Mutation Taster
=77/23
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs145252614; hg19: chr1-101377789; COSMIC: COSV63016994; API