7-66092862-G-T
Variant names:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000048.4(ASL):c.1345G>T(p.Asp449Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,266 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )
Consequence
ASL
NM_000048.4 missense
NM_000048.4 missense
Scores
1
9
9
Clinical Significance
Not reported in ClinVar
Conservation
PhyloP100: 1.52
Genes affected
ASL (HGNC:746): (argininosuccinate lyase) This gene encodes a member of the lyase 1 family. The encoded protein forms a cytosolic homotetramer and primarily catalyzes the reversible hydrolytic cleavage of argininosuccinate into arginine and fumarate, an essential step in the liver in detoxifying ammonia via the urea cycle. Mutations in this gene result in the autosomal recessive disorder argininosuccinic aciduria, or argininosuccinic acid lyase deficiency. A nontranscribed pseudogene is also located on the long arm of chromosome 22. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
ASL | NM_000048.4 | c.1345G>T | p.Asp449Tyr | missense_variant | Exon 17 of 17 | ENST00000304874.14 | NP_000039.2 | |
ASL | NM_001024943.2 | c.1345G>T | p.Asp449Tyr | missense_variant | Exon 16 of 16 | NP_001020114.1 | ||
ASL | NM_001024944.2 | c.1285G>T | p.Asp429Tyr | missense_variant | Exon 15 of 15 | NP_001020115.1 | ||
ASL | NM_001024946.2 | c.1267G>T | p.Asp423Tyr | missense_variant | Exon 15 of 15 | NP_001020117.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
ASL | ENST00000304874.14 | c.1345G>T | p.Asp449Tyr | missense_variant | Exon 17 of 17 | 1 | NM_000048.4 | ENSP00000307188.9 | ||
ENSG00000249319 | ENST00000450043.2 | c.563+199G>T | intron_variant | Intron 7 of 11 | 5 | ENSP00000396527.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460266Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 726506
GnomAD4 exome
AF:
AC:
1
AN:
1460266
Hom.:
Cov.:
32
AF XY:
AC XY:
0
AN XY:
726506
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 Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Not reported inComputational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Benign
DANN
Benign
DEOGEN2
Uncertain
T;.;T;.
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Uncertain
.;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
L;.;L;.
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;N;N
REVEL
Uncertain
Sift
Benign
T;T;T;T
Sift4G
Uncertain
D;D;D;D
Polyphen
P;.;P;.
Vest4
MutPred
Gain of MoRF binding (P = 0.0673);.;Gain of MoRF binding (P = 0.0673);.;
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
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
No publications associated with this variant yet.