dbSNP rs140064577: ADSL:p.Asp6Asn (chr22-40346574-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_000026.4(ADSL):c.16G>A(p.Asp6Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,452,924 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

ADSL
NM_000026.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.61

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]

ADSL links:

ENSG00000284431 (HGNC:):

ENSG00000284431 links:

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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=0.10470447).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ADSL	NM_000026.4 link	c.16G>A	p.Asp6Asn	missense_variant	Exon 1 of 13	ENST00000623063.3	NP_000017.1	P30566-1X5D8S6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ADSL	ENST00000623063.3 link	c.16G>A	p.Asp6Asn	missense_variant	Exon 1 of 13	1	NM_000026.4	ENSP00000485525.1		P30566-1
ENSG00000284431	ENST00000639722.1 link	n.16G>A		non_coding_transcript_exon_variant	Exon 1 of 31	5		ENSP00000492828.1		A0A1W2PRX2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1452924

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

722250

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:

0.0000118

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.02e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.012

T;T;.;T;T;T;.

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.83

FATHMM_MKL

Benign

0.69

LIST_S2

Uncertain

0.91

D;D;D;D;D;D;D

M_CAP

Pathogenic

0.31

MetaRNN

Benign

0.10

T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.052

MutationAssessor

Benign

0.90

.;L;L;.;.;.;.

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-0.39

.;.;N;.;N;.;.

REVEL

Benign

0.17

Sift

Benign

0.060

.;.;T;.;T;.;.

Sift4G

Uncertain

0.028

D;D;D;.;D;.;.

Polyphen

0.0040, 0.0020

.;B;B;.;.;.;.

Vest4

0.29, 0.27, 0.32

MutPred

0.11

Gain of catalytic residue at S9 (P = 0.1631);Gain of catalytic residue at S9 (P = 0.1631);Gain of catalytic residue at S9 (P = 0.1631);Gain of catalytic residue at S9 (P = 0.1631);Gain of catalytic residue at S9 (P = 0.1631);Gain of catalytic residue at S9 (P = 0.1631);Gain of catalytic residue at S9 (P = 0.1631);

MVP

0.90

MPC

0.29

ClinPred

0.17

GERP RS

1.3

Varity_R

0.29

gMVP

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over