rs386833794
Variant summary
Our verdict is Pathogenic. The variant received 18 ACMG points: 18P and 0B. PVS1PM2PP5_Very_Strong
The NM_003982.4(SLC7A7):c.1005_1008delCTTT(p.Phe335LeufsTer15) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,036 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
SLC7A7
NM_003982.4 frameshift
NM_003982.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.32
Publications
1 publications found
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]
SLC7A7 Gene-Disease associations (from GenCC):
- lysinuric protein intoleranceInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics, ClinGen, Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 18 ACMG points.
PVS1
Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 14-22775530-CAAAG-C is Pathogenic according to our data. Variant chr14-22775530-CAAAG-C is described in ClinVar as Pathogenic/Likely_pathogenic. ClinVar VariationId is 56346.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_003982.4. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLC7A7 | MANE Select | c.1005_1008delCTTT | p.Phe335LeufsTer15 | frameshift | Exon 7 of 10 | NP_003973.3 | |||
| SLC7A7 | c.1005_1008delCTTT | p.Phe335LeufsTer15 | frameshift | Exon 8 of 11 | NP_001119577.1 | A0A0S2Z502 | |||
| SLC7A7 | c.1005_1008delCTTT | p.Phe335LeufsTer15 | frameshift | Exon 8 of 11 | NP_001119578.1 | Q9UM01 |
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| SLC7A7 | MANE Select | c.1005_1008delCTTT | p.Phe335LeufsTer15 | frameshift | Exon 7 of 10 | ENSP00000501493.1 | Q9UM01 | ||
| SLC7A7 | TSL:1 | c.1005_1008delCTTT | p.Phe335LeufsTer15 | frameshift | Exon 8 of 11 | ENSP00000380662.4 | Q9UM01 | ||
| SLC7A7 | TSL:1 | c.1005_1008delCTTT | p.Phe335LeufsTer15 | frameshift | Exon 7 of 10 | ENSP00000380663.2 | Q9UM01 |
Frequencies
GnomAD3 genomes 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 33 show subpopulations
GnomAD3 genomes
AF:
AC:
1
AN:
152184
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
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Gnomad SAS
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Gnomad FIN
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Gnomad MID
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Gnomad NFE
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Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000205 AC: 3AN: 1461852Hom.: 0 AF XY: 0.00000275 AC XY: 2AN XY: 727226 show subpopulations
GnomAD4 exome
AF:
AC:
3
AN:
1461852
Hom.:
AF XY:
AC XY:
2
AN XY:
727226
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33476
American (AMR)
AF:
AC:
0
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53414
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
2
AN:
1111986
Other (OTH)
AF:
AC:
1
AN:
60390
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
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2
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0.95
Allele balance
Age Distribution
Exome Het
Variant carriers
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Age
GnomAD4 genome 0.00000657 AC: 1AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74344 show subpopulations
GnomAD4 genome
AF:
AC:
1
AN:
152184
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74344
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41430
American (AMR)
AF:
AC:
0
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3470
East Asian (EAS)
AF:
AC:
0
AN:
5206
South Asian (SAS)
AF:
AC:
0
AN:
4832
European-Finnish (FIN)
AF:
AC:
1
AN:
10612
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68038
Other (OTH)
AF:
AC:
0
AN:
2088
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.675
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
ClinVar
ClinVar submissions
View on ClinVar Significance:Pathogenic/Likely pathogenic
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
6
-
-
Lysinuric protein intolerance (6)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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