5-1216947-T-C
Position:
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PM2PP3_Strong
The NM_001003841.3(SLC6A19):c.1173+2T>C variant causes a splice donor change. The variant allele was found at a frequency of 0.00000434 in 1,612,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 35)
Exomes 𝑓: 0.0000034 ( 0 hom. )
Consequence
SLC6A19
NM_001003841.3 splice_donor
NM_001003841.3 splice_donor
Scores
1
3
3
Splicing: ADA: 0.9651
1
1
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 5.46
Genes affected
SLC6A19 (HGNC:27960): (solute carrier family 6 member 19) This gene encodes a system B(0) transmembrane protein that actively transports most neutral amino acids across the apical membrane of epithelial cells. Mutations in this gene may result in Hartnup disorder, an inherited disease with symptoms such as pellagra, cerebellar ataxia, and psychosis. The expression and function of B0AT1 (SLC6A19) in intestinal cells depends on the presence of the accessory protein angiotensin-converting enzyme 2 (ACE2) which, among other functions, acts as a chaperone for membrane trafficking of B0AT1. The ACE2 is also the cellular receptor for severe acute respiratory syndrome-coronavirus (SARS-CoV) and for SARS-CoV-2 that is causing the coronavirus 2019 (COVID-19) pandemic [provided by RefSeq, Jul 2020]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
Splicing variant, LoF is a know mechanism of disease, No cryptic splice site detected. Exon removal results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP3
BayesDel_addAF computational evidence supports a deleterious effect, 0.499
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SLC6A19 | NM_001003841.3 | c.1173+2T>C | splice_donor_variant | ENST00000304460.11 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SLC6A19 | ENST00000304460.11 | c.1173+2T>C | splice_donor_variant | 1 | NM_001003841.3 | P1 | |||
SLC6A19 | ENST00000515652.5 | c.*118+2T>C | splice_donor_variant, NMD_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 35
GnomAD3 genomes
AF:
AC:
2
AN:
152220
Hom.:
Cov.:
35
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000801 AC: 2AN: 249668Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135256
GnomAD3 exomes
AF:
AC:
2
AN:
249668
Hom.:
AF XY:
AC XY:
1
AN XY:
135256
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1460188Hom.: 0 Cov.: 36 AF XY: 0.00000413 AC XY: 3AN XY: 726400
GnomAD4 exome
AF:
AC:
5
AN:
1460188
Hom.:
Cov.:
36
AF XY:
AC XY:
3
AN XY:
726400
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000131 AC: 2AN: 152220Hom.: 0 Cov.: 35 AF XY: 0.0000134 AC XY: 1AN XY: 74366
GnomAD4 genome
AF:
AC:
2
AN:
152220
Hom.:
Cov.:
35
AF XY:
AC XY:
1
AN XY:
74366
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ExAC
AF:
AC:
1
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
MutationTaster
Benign
D
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: 2
DS_DL_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at