Variant 3-151757113-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_207365.4(AADACL2):c.725C>T(p.Thr242Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000682 in 1,612,830 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

AADACL2
NM_207365.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.20

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
AADACL2	NM_207365.4 linkuse as main transcript	c.725C>T	p.Thr242Ile	missense_variant	5/5	ENST00000356517.4	NP_997248.2
AADACL2-AS1	NR_110203.1 linkuse as main transcript	n.380-5602G>A		intron_variant, non_coding_transcript_variant
AADACL2-AS1	NR_110202.1 linkuse as main transcript	n.380-1982G>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.725C>T	p.Thr242Ile	missense_variant	5/5	1	NM_207365.4	ENSP00000348911	P1	Q6P093-1
AADACL2	ENST00000445270.1 linkuse as main transcript	c.*340C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	1		ENSP00000387390
AADACL2-AS1	ENST00000483843.6 linkuse as main transcript	n.500-1982G>A		intron_variant, non_coding_transcript_variant		5
AADACL2-AS1	ENST00000475855.1 linkuse as main transcript	n.380-1982G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151376

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251032

Hom.:

AF XY:

0.00000737

AC XY:

AN XY:

135712

show subpopulations

Gnomad AFR exome

AF:

0.0000618

Gnomad AMR exome

AF:

0.00

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:

0.00000411

AC:

AN:

1461454

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727042

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

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:

0.00

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151376

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73874

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000642

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

Aug 16, 2022

The c.725C>T (p.T242I) 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 725, causing the threonine (T) at amino acid position 242 to be replaced by an isoleucine (I). 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

Pathogenic

0.61

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.0020

MetaRNN

Uncertain

0.43

MetaSVM

Benign

-0.91

MutationAssessor

Pathogenic

3.6

MutationTaster

Benign

0.92

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.6

REVEL

Benign

0.19

Sift

Uncertain

0.0080

Sift4G

Benign

0.39

Polyphen

0.91

Vest4

0.14

MutPred

0.65

Loss of loop (P = 0.0203);

MVP

0.072

MPC

0.31

ClinPred

0.80

GERP RS

4.8

Varity_R

0.58

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