chr6-33201397-A-T

Variant summary

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

The NM_006979.3(SLC39A7):​c.152A>T​(p.His51Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SLC39A7
NM_006979.3 missense

Scores

5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.44
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]

Genome browser will be placed here

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=0.15838534).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC39A7NM_006979.3 linkuse as main transcriptc.152A>T p.His51Leu missense_variant 1/7 ENST00000374677.8 NP_008910.2
SLC39A7NM_001077516.2 linkuse as main transcriptc.152A>T p.His51Leu missense_variant 2/8 NP_001070984.1
SLC39A7NM_001288777.2 linkuse as main transcriptc.52+9A>T intron_variant NP_001275706.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC39A7ENST00000374677.8 linkuse as main transcriptc.152A>T p.His51Leu missense_variant 1/71 NM_006979.3 ENSP00000363809 P1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.0000280
AC:
7
AN:
249572
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135408
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000579
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000883
Gnomad OTH exome
AF:
0.000659
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461828
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
727222
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.000112
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32
ExAC
AF:
0.0000248
AC:
3

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), LabcorpAug 09, 2022In 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 missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals affected with SLC39A7-related conditions. This variant is present in population databases (rs763865179, gnomAD 0.003%). This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 51 of the SLC39A7 protein (p.His51Leu). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.16
BayesDel_addAF
Benign
-0.084
T
BayesDel_noAF
Benign
-0.28
CADD
Benign
22
DANN
Benign
0.94
DEOGEN2
Benign
0.070
T;T
Eigen
Benign
-0.35
Eigen_PC
Benign
-0.18
FATHMM_MKL
Uncertain
0.81
D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.8
L;L
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-2.4
N;N
REVEL
Benign
0.095
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.013
D;D
Polyphen
0.079
B;B
Vest4
0.38
MutPred
0.26
Loss of loop (P = 0.0804);Loss of loop (P = 0.0804);
MVP
0.56
MPC
0.55
ClinPred
0.18
T
GERP RS
4.5
Varity_R
0.21
gMVP
0.56

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

LitVar

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

Other links and lift over

dbSNP: rs763865179; hg19: chr6-33169174; API