8-17543422-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001370338.1(SLC7A2):​c.83C>T​(p.Thr28Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000205 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SLC7A2
NM_001370338.1 missense

Scores

2
7
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.13
Variant links:
Genes affected
SLC7A2 (HGNC:11060): (solute carrier family 7 member 2) The protein encoded by this gene is a cationic amino acid transporter and a member of the APC (amino acid-polyamine-organocation) family of transporters. The encoded membrane protein is responsible for the cellular uptake of arginine, lysine and ornithine. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.36793482).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SLC7A2NM_001370338.1 linkc.83C>T p.Thr28Ile missense_variant Exon 3 of 13 ENST00000494857.6 NP_001357267.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SLC7A2ENST00000494857.6 linkc.83C>T p.Thr28Ile missense_variant Exon 3 of 13 5 NM_001370338.1 ENSP00000419140.2 P52569-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251420
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
135876
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000289
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:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000205
AC:
3
AN:
1461894
Hom.:
0
Cov.:
32
AF XY:
0.00000275
AC XY:
2
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000447
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
Bravo
AF:
0.0000151

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 05, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.203C>T (p.T68I) alteration is located in exon 2 (coding exon 2) of the SLC7A2 gene. This alteration results from a C to T substitution at nucleotide position 203, causing the threonine (T) at amino acid position 68 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
0.58
BayesDel_addAF
Benign
-0.085
T
BayesDel_noAF
Benign
-0.28
CADD
Uncertain
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.37
T;T;.;.;.;.
Eigen
Benign
0.14
Eigen_PC
Uncertain
0.30
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.95
.;D;.;D;D;D
M_CAP
Benign
0.037
D
MetaRNN
Benign
0.37
T;T;T;T;T;T
MetaSVM
Uncertain
0.14
D
MutationAssessor
Benign
0.34
N;N;.;.;.;.
PrimateAI
Benign
0.47
T
PROVEAN
Uncertain
-3.4
D;D;D;D;D;.
REVEL
Uncertain
0.36
Sift
Benign
0.074
T;T;T;T;T;.
Sift4G
Uncertain
0.055
T;T;T;T;T;.
Polyphen
0.21
B;B;P;B;P;.
Vest4
0.15
MutPred
0.41
Loss of ubiquitination at K29 (P = 0.1166);Loss of ubiquitination at K29 (P = 0.1166);.;.;.;.;
MVP
0.95
MPC
0.048
ClinPred
0.63
D
GERP RS
5.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.16
gMVP
0.47

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: rs1327292229; hg19: chr8-17400931; API