GeneBe

rs11089991

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000026.4(ADSL):ā€‹c.440A>Gā€‹(p.Lys147Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,872 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. K147M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

ADSL
NM_000026.4 missense

Scores

2
5
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 4.97
Variant links:
Genes affected
ADSL (HGNC:291): (adenylosuccinate lyase) The protein encoded by this gene belongs to the lyase 1 family. It is an essential enzyme involved in purine metabolism, and catalyzes two non-sequential reactions in the de novo purine biosynthetic pathway: the conversion of succinylaminoimidazole carboxamide ribotide (SAICAR) to aminoimidazole carboxamide ribotide (AICAR) and the conversion of adenylosuccinate (S-AMP) to adenosine monophosphate (AMP). Mutations in this gene are associated with adenylosuccinase deficiency (ADSLD), a disorder marked with psychomotor retardation, epilepsy or autistic features. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.26040277).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ADSLNM_000026.4 linkc.440A>G p.Lys147Arg missense_variant Exon 4 of 13 ENST00000623063.3 NP_000017.1 P30566-1X5D8S6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ADSLENST00000623063.3 linkc.440A>G p.Lys147Arg missense_variant Exon 4 of 13 1 NM_000026.4 ENSP00000485525.1 P30566-1
ENSG00000284431ENST00000639722.1 linkn.*178+4250A>G intron_variant Intron 3 of 30 5 ENSP00000492828.1 A0A1W2PRX2

Frequencies

GnomAD3 genomes
Cov.:
31
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461872
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727238
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:
0.0000331
GnomAD4 genome
Cov.:
31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.074
BayesDel_addAF
Uncertain
0.044
T
BayesDel_noAF
Benign
-0.17
CADD
Benign
21
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0076
T;T;.;T;T;T;.
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.022
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Uncertain
0.90
D;D;D;D;D;D;D
M_CAP
Uncertain
0.24
D
MetaRNN
Benign
0.26
T;T;T;T;T;T;T
MetaSVM
Pathogenic
0.85
D
MutationAssessor
Benign
0.97
.;L;L;.;.;.;.
PrimateAI
Benign
0.35
T
PROVEAN
Benign
-0.89
.;.;N;.;.;.;.
REVEL
Uncertain
0.38
Sift
Benign
0.54
.;.;T;.;.;.;.
Sift4G
Benign
0.56
T;T;T;.;T;.;.
Polyphen
0.0010, 0.0
.;B;B;.;.;.;.
Vest4
0.23, 0.26, 0.29
MutPred
0.29
.;.;.;.;Loss of ubiquitination at K161 (P = 0.0244);.;.;
MVP
0.96
MPC
0.25
ClinPred
0.43
T
GERP RS
3.6
Varity_R
0.19
gMVP
0.69

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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: chr22-40750289; API