Variant 1-12666025-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001013630.2(AADACL4):c.514C>G(p.His172Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00305 in 1,614,202 control chromosomes in the GnomAD database, including 22 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0025 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0031 ( 19 hom. )

Consequence

AADACL4
NM_001013630.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.92

Variant links:

Genes affected

AADACL4 (HGNC:32038): (arylacetamide deacetylase like 4) Predicted to enable hydrolase activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

AADACL4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012014955).

BP6

Variant 1-12666025-C-G is Benign according to our data. Variant chr1-12666025-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2638256.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AADACL4	NM_001013630.2 linkuse as main transcript	c.514C>G	p.His172Asp	missense_variant	4/4	ENST00000376221.2	NP_001013652.1	Q5VUY2
AADACL4	XM_017001153.1 linkuse as main transcript	c.16C>G	p.His6Asp	missense_variant	2/2		XP_016856642.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AADACL4	ENST00000376221.2 linkuse as main transcript	c.514C>G	p.His172Asp	missense_variant	4/4	5	NM_001013630.2	ENSP00000365395.1		Q5VUY2

Frequencies

GnomAD3 genomes

AF:

0.00253

AC:

385

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000651

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.0167

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.00319

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00266

AC:

669

AN:

251298

Hom.:

AF XY:

0.00281

AC XY:

381

AN XY:

135800

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.00182

Gnomad ASJ exome

AF:

0.0168

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00108

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.00327

Gnomad OTH exome

AF:

0.00392

GnomAD4 exome

AF:

0.00310

AC:

4534

AN:

1461844

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

2326

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.000747

Gnomad4 AMR exome

AF:

0.00183

Gnomad4 ASJ exome

AF:

0.0193

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00146

Gnomad4 FIN exome

AF:

0.0000562

Gnomad4 NFE exome

AF:

0.00306

Gnomad4 OTH exome

AF:

0.00517

GnomAD4 genome

AF:

0.00253

AC:

385

AN:

152358

Hom.:

Cov.:

AF XY:

0.00267

AC XY:

199

AN XY:

74498

show subpopulations

Gnomad4 AFR

AF:

0.000649

Gnomad4 AMR

AF:

0.00411

Gnomad4 ASJ

AF:

0.0167

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00228

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00319

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00427

Hom.:

Bravo

AF:

0.00269

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00467

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00241

AC:

292

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00518

EpiControl

AF:

0.00433

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

AADACL4: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.23

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.18

Eigen

Benign

-0.46

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.57

LIST_S2

Benign

0.73

M_CAP

Benign

0.015

MetaRNN

Benign

0.012

MetaSVM

Benign

-0.84

MutationAssessor

Pathogenic

3.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.41

PROVEAN

Pathogenic

-7.5

REVEL

Benign

0.23

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0030

Polyphen

1.0

Vest4

0.70

MVP

0.43

MPC

0.15

ClinPred

0.11

GERP RS

-1.4

Varity_R

0.89

gMVP

0.68

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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