6-33201393-T-C

Variant summary

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

The NM_006979.3(SLC39A7):ā€‹c.148T>Cā€‹(p.Ser50Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000372 in 1,613,782 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 (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

SLC39A7
NM_006979.3 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 0.121
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=0.15766546).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC39A7NM_006979.3 linkuse as main transcriptc.148T>C p.Ser50Pro missense_variant 1/7 ENST00000374677.8 NP_008910.2
SLC39A7NM_001077516.2 linkuse as main transcriptc.148T>C p.Ser50Pro missense_variant 2/8 NP_001070984.1
SLC39A7NM_001288777.2 linkuse as main transcriptc.52+5T>C splice_donor_5th_base_variant, intron_variant NP_001275706.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC39A7ENST00000374677.8 linkuse as main transcriptc.148T>C p.Ser50Pro missense_variant 1/71 NM_006979.3 ENSP00000363809 P1

Frequencies

GnomAD3 genomes
AF:
0.00000658
AC:
1
AN:
151966
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000401
AC:
1
AN:
249572
Hom.:
0
AF XY:
0.00000739
AC XY:
1
AN XY:
135406
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461816
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000232
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000658
AC:
1
AN:
151966
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74224
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000113
ExAC
AF:
0.00000825
AC:
1
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsSep 29, 2023The c.148T>C (p.S50P) alteration is located in exon 1 (coding exon 1) of the SLC39A7 gene. This alteration results from a T to C substitution at nucleotide position 148, causing the serine (S) at amino acid position 50 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpJun 02, 2022This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 50 of the SLC39A7 protein (p.Ser50Pro). This variant is present in population databases (rs762338940, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with SLC39A7-related conditions. ClinVar contains an entry for this variant (Variation ID: 1409049). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In 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. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.10
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.35
CADD
Benign
21
DANN
Uncertain
0.97
DEOGEN2
Benign
0.0057
T;T
Eigen
Benign
-0.18
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.25
N
M_CAP
Benign
0.019
T
MetaRNN
Benign
0.16
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.4
L;L
MutationTaster
Benign
0.94
D;D
PrimateAI
Uncertain
0.50
T
PROVEAN
Benign
-0.92
N;N
REVEL
Benign
0.14
Sift
Benign
0.066
T;T
Sift4G
Benign
0.34
T;T
Polyphen
0.83
P;P
Vest4
0.23
MutPred
0.097
Loss of phosphorylation at S50 (P = 0.0256);Loss of phosphorylation at S50 (P = 0.0256);
MVP
0.62
MPC
0.56
ClinPred
0.34
T
GERP RS
4.5
Varity_R
0.19
gMVP
0.38

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: rs762338940; hg19: chr6-33169170; API