chr6-33201250-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006979.3(SLC39A7):​c.5C>T​(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

SLC39A7
NM_006979.3 missense

Scores

4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.757
Variant links:
Genes affected
SLC39A7 (HGNC:4927): (solute carrier family 39 member 7) The protein encoded by this gene transports zinc from the Golgi and endoplasmic reticulum to the cytoplasm. This transport may be important for activation of tyrosine kinases, some of which could be involved in cancer progression. Therefore, modulation of the encoded protein could be useful as a therapeutic agent against cancer. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2014]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.18515697).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC39A7NM_006979.3 linkuse as main transcriptc.5C>T p.Ala2Val missense_variant 1/7 ENST00000374677.8 NP_008910.2
SLC39A7NM_001077516.2 linkuse as main transcriptc.5C>T p.Ala2Val missense_variant 2/8 NP_001070984.1
SLC39A7NM_001288777.2 linkuse as main transcriptc.-87C>T 5_prime_UTR_variant 2/8 NP_001275706.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC39A7ENST00000374677.8 linkuse as main transcriptc.5C>T p.Ala2Val missense_variant 1/71 NM_006979.3 ENSP00000363809 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpOct 19, 2020In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SLC39A7-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with valine at codon 2 of the SLC39A7 protein (p.Ala2Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.042
T
BayesDel_noAF
Benign
-0.30
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0041
T;T
Eigen
Benign
-0.25
Eigen_PC
Benign
-0.086
FATHMM_MKL
Benign
0.14
N
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.19
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.4
L;L
MutationTaster
Benign
1.0
N;N
PrimateAI
Uncertain
0.77
T
PROVEAN
Benign
-0.79
N;N
REVEL
Benign
0.16
Sift
Uncertain
0.0070
D;D
Sift4G
Uncertain
0.050
T;T
Polyphen
0.018
B;B
Vest4
0.27
MutPred
0.36
Loss of disorder (P = 0.1168);Loss of disorder (P = 0.1168);
MVP
0.59
MPC
0.44
ClinPred
0.61
D
GERP RS
4.3
RBP_binding_hub_radar
0.97
RBP_regulation_power_radar
2.1
Varity_R
0.077
gMVP
0.31

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs1774517817; hg19: chr6-33169027; API