rs183697499

Variant names:

• chr3-151740821-G-A
• rs183697499
• NM_207365.4:c.314G>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_207365.4(AADACL2):​c.314G>A​(p.Arg105Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000867 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000076 (0 hom.)
• Consequence: AADACL2 NM_207365.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.03
• Publications: 2 publications found

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_207365.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AADACL2	NM_207365.4	MANE Select	c.314G>A	p.Arg105Gln	missense	Exon 2 of 5	NP_997248.2	Q6P093-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AADACL2	ENST00000356517.4	TSL:1 MANE Select	c.314G>A	p.Arg105Gln	missense	Exon 2 of 5	ENSP00000348911.3	Q6P093-1
	AADACL2	ENST00000445270.1	TSL:1	n.139-3272G>A		intron	N/A	ENSP00000387390.1	F8WFE5
	AADACL2-AS1	ENST00000754423.1		n.451+10622C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.000191 AC: 29 AN: 152162 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000588

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.0000915 AC: 23 AN: 251234 AF XY: 0.0000958

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000202

Gnomad ASJ exome AF: 0.000695

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000704

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000759 AC: 111 AN: 1461724 Hom.: 0 Cov.: 31 AF XY: 0.0000743 AC XY: 54 AN XY: 727162

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.000224 AC: 10 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.000689 AC: 18 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39652

South Asian (SAS) AF: 0.0000928 AC: 8 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5762

European-Non Finnish (NFE) AF: 0.0000567 AC: 63 AN: 1111942

Other (OTH) AF: 0.000166 AC: 10 AN: 60386

GnomAD4 genome AF: 0.000190 AC: 29 AN: 152282 Hom.: 0 Cov.: 33 AF XY: 0.000201 AC XY: 15 AN XY: 74468

African (AFR) AF: 0.0000481 AC: 2 AN: 41568

American (AMR) AF: 0.00111 AC: 17 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000588 AC: 4 AN: 68006

Other (OTH) AF: 0.00142 AC: 3 AN: 2106

Alfa AF: 0.000176 Hom.: 0

Bravo AF: 0.000442

ExAC AF: 0.0000824 AC: 10

EpiCase AF: 0.0000546

EpiControl AF: 0.000178

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.58	D
M_CAP	Benign	0.0063	T
MetaRNN	Benign	0.075	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		2.0
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.25
Sift	Benign	0.039	D
Sift4G	Benign	0.097	T
Polyphen		0.92	P
Vest4		0.42
MVP		0.17
MPC		0.079
ClinPred		0.18	T
GERP RS		-0.97
Varity_R		0.34
gMVP		0.46
Mutation Taster		=95/5	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.24		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.24		Position offset: -3

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs183697499; hg19: chr3-151458609; COSMIC: COSV62929757;