3-151745634-C-A

Variant names:

• chr3-151745634-C-A
• rs138796090
• NM_207365.4:c.557C>A

Variant summary

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

The NM_207365.4(AADACL2):​c.557C>A​(p.Ala186Glu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A186S) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AADACL2 NM_207365.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.62

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]

ACMG classification

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 rank	MANE	Protein	UniProt
AADACL2	NM_207365.4	c.557C>A	p.Ala186Glu	missense_variant	Exon 4 of 5	ENST00000356517.4	NP_997248.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AADACL2	ENST00000356517.4	c.557C>A	p.Ala186Glu	missense_variant	Exon 4 of 5	1	NM_207365.4	ENSP00000348911.3
AADACL2	ENST00000445270.1	n.*172C>A		non_coding_transcript_exon_variant	Exon 3 of 4	1		ENSP00000387390.1
AADACL2	ENST00000445270.1	n.*172C>A		3_prime_UTR_variant	Exon 3 of 4	1		ENSP00000387390.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	19
DANN	Benign	0.90
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.30
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.0096	T
MetaRNN	Uncertain	0.69	D
MetaSVM	Benign	-0.56	T
MutationAssessor	Pathogenic	3.4	M
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.36
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.012	D
Polyphen		0.30	B
Vest4		0.66
MutPred		0.61		Loss of glycosylation at S190 (P = 0.0234);
MVP		0.22
MPC		0.14
ClinPred		0.95	D
GERP RS		2.8
Varity_R		0.66
gMVP		0.59

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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

Other links and lift over

dbSNP: rs138796090; hg19: chr3-151463422;