chr14-22813086-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_003982.4(SLC7A7):c.313G>A(p.Ala105Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000186 in 1,614,058 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SLC7A7
NM_003982.4 missense
NM_003982.4 missense
Scores
8
8
2
Clinical Significance
Conservation
PhyloP100: 7.91
Genes affected
SLC7A7 (HGNC:11065): (solute carrier family 7 member 7) The protein encoded by this gene is the light subunit of a cationic amino acid transporter. This sodium-independent transporter is formed when the light subunit encoded by this gene dimerizes with the heavy subunit transporter protein SLC3A2. This transporter is found in epithelial cell membranes where it transfers cationic and large neutral amino acids from the cell to the extracellular space. Defects in this gene are a cause of lysinuric protein intolerance (LPI). Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2011]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.861
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC7A7 | NM_003982.4 | c.313G>A | p.Ala105Thr | missense_variant | 2/10 | ENST00000674313.1 | |
SLC7A7 | NM_001126105.3 | c.313G>A | p.Ala105Thr | missense_variant | 3/11 | ||
SLC7A7 | NM_001126106.4 | c.313G>A | p.Ala105Thr | missense_variant | 3/11 | ||
SLC7A7 | XM_011537299.2 | c.313G>A | p.Ala105Thr | missense_variant | 2/10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC7A7 | ENST00000674313.1 | c.313G>A | p.Ala105Thr | missense_variant | 2/10 | NM_003982.4 | P1 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251042Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135744
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461894Hom.: 0 Cov.: 70 AF XY: 0.00000138 AC XY: 1AN XY: 727248
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152164Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1AN XY: 74328
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Lysinuric protein intolerance Uncertain:3
Uncertain significance, no assertion criteria provided | clinical testing | Natera, Inc. | Dec 31, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 31, 2021 | This sequence change replaces alanine with threonine at codon 105 of the SLC7A7 protein (p.Ala105Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs775943127, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with SLC7A7-related conditions. 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 18, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D;D;D;D;D;D;.;D;.;D;D
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Uncertain
D
M_CAP
Uncertain
D
MetaRNN
Pathogenic
D;D;D;D;D;D;D;D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
M;M;M;M;M;.;.;.;.;.;.
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;D;D;D;D;D;D;D
REVEL
Pathogenic
Sift
Uncertain
D;D;D;D;D;D;D;T;D;D;D
Sift4G
Benign
T;T;T;T;T;.;.;.;.;.;.
Polyphen
D;D;D;D;D;.;.;.;.;.;.
Vest4
MutPred
Loss of stability (P = 0.0722);Loss of stability (P = 0.0722);Loss of stability (P = 0.0722);Loss of stability (P = 0.0722);Loss of stability (P = 0.0722);Loss of stability (P = 0.0722);Loss of stability (P = 0.0722);Loss of stability (P = 0.0722);Loss of stability (P = 0.0722);Loss of stability (P = 0.0722);Loss of stability (P = 0.0722);
MVP
MPC
0.72
ClinPred
D
GERP RS
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Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at