7-66092862-G-T

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

Scores

1
9
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.52
Variant links:
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
ASLNM_000048.4 linkc.1345G>T p.Asp449Tyr missense_variant Exon 17 of 17 ENST00000304874.14 NP_000039.2 P04424-1A0A024RDL8
ASLNM_001024943.2 linkc.1345G>T p.Asp449Tyr missense_variant Exon 16 of 16 NP_001020114.1 P04424-1A0A024RDL8
ASLNM_001024944.2 linkc.1285G>T p.Asp429Tyr missense_variant Exon 15 of 15 NP_001020115.1 P04424-2
ASLNM_001024946.2 linkc.1267G>T p.Asp423Tyr missense_variant Exon 15 of 15 NP_001020117.1 A0A0S2Z316

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ASLENST00000304874.14 linkc.1345G>T p.Asp449Tyr missense_variant Exon 17 of 17 1 NM_000048.4 ENSP00000307188.9 P04424-1
ENSG00000249319ENST00000450043.2 linkc.563+199G>T intron_variant Intron 7 of 11 5 ENSP00000396527.2 H7C0S8

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1460266
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
726506
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Uncertain
0.15
D
BayesDel_noAF
Uncertain
-0.020
CADD
Benign
21
DANN
Benign
0.86
DEOGEN2
Uncertain
0.47
T;.;T;.
Eigen
Benign
-0.10
Eigen_PC
Benign
-0.12
FATHMM_MKL
Benign
0.46
N
LIST_S2
Uncertain
0.96
.;D;D;D
M_CAP
Pathogenic
0.95
D
MetaRNN
Uncertain
0.47
T;T;T;T
MetaSVM
Uncertain
0.74
D
MutationAssessor
Benign
1.7
L;.;L;.
PrimateAI
Uncertain
0.53
T
PROVEAN
Benign
-0.30
N;N;N;N
REVEL
Uncertain
0.46
Sift
Benign
0.15
T;T;T;T
Sift4G
Uncertain
0.037
D;D;D;D
Polyphen
0.91
P;.;P;.
Vest4
0.27
MutPred
0.38
Gain of MoRF binding (P = 0.0673);.;Gain of MoRF binding (P = 0.0673);.;
MVP
0.94
MPC
0.52
ClinPred
0.23
T
GERP RS
4.7
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.070
gMVP
0.68

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-65557849; API