Variant chr3-151757353-C-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_207365.4(AADACL2):c.965C>T(p.Ala322Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000547 in 1,461,556 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

AADACL2
NM_207365.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.10

Variant links:

Genes affected

AADACL2 (HGNC:24427): (arylacetamide deacetylase like 2) Predicted to enable hydrolase activity. Predicted to be located in extracellular region. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

AADACL2 links:

AADACL2-AS1 (HGNC:50301): (AADACL2 antisense RNA 1)

AADACL2-AS1 links:

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=0.14872187).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AADACL2	NM_207365.4 linkuse as main transcript	c.965C>T	p.Ala322Val	missense_variant	5/5	ENST00000356517.4	NP_997248.2
AADACL2-AS1	NR_110203.1 linkuse as main transcript	n.380-5842G>A		intron_variant, non_coding_transcript_variant
AADACL2-AS1	NR_110202.1 linkuse as main transcript	n.380-2222G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AADACL2	ENST00000356517.4 linkuse as main transcript	c.965C>T	p.Ala322Val	missense_variant	5/5	1	NM_207365.4	ENSP00000348911	P1	Q6P093-1
AADACL2	ENST00000445270.1 linkuse as main transcript	c.*580C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	1		ENSP00000387390
AADACL2-AS1	ENST00000483843.6 linkuse as main transcript	n.500-2222G>A		intron_variant, non_coding_transcript_variant		5
AADACL2-AS1	ENST00000475855.1 linkuse as main transcript	n.380-2222G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000279

AC:

AN:

250980

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000547

AC:

AN:

1461556

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

727084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000157

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 18, 2024

The c.965C>T (p.A322V) alteration is located in exon 5 (coding exon 5) of the AADACL2 gene. This alteration results from a C to T substitution at nucleotide position 965, causing the alanine (A) at amino acid position 322 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.095

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.12

M_CAP

Benign

0.0014

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.5

REVEL

Benign

0.075

Sift

Benign

0.28

Sift4G

Benign

0.29

Polyphen

0.72

Vest4

0.11

MutPred

0.75

Loss of glycosylation at P319 (P = 0.0723);

MVP

0.048

MPC

0.12

ClinPred

0.42

GERP RS

2.2

Varity_R

0.062

gMVP

0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over