3-151745615-C-A

Variant names:

• chr3-151745615-C-A
• rs200688205
• NM_207365.4:c.538C>A

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_207365.4(AADACL2):​c.538C>A​(p.Pro180Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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. P180S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AADACL2 NM_207365.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.39
• Publications: 0 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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.868

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.538C>A	p.Pro180Thr	missense	Exon 4 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.538C>A	p.Pro180Thr	missense	Exon 4 of 5	ENSP00000348911.3	Q6P093-1
	AADACL2	ENST00000445270.1	TSL:1	n.*153C>A		non_coding_transcript_exon	Exon 3 of 4	ENSP00000387390.1	F8WFE5
	AADACL2	ENST00000445270.1	TSL:1	n.*153C>A		3_prime_UTR	Exon 3 of 4	ENSP00000387390.1	F8WFE5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Pathogenic	0.29	D
BayesDel_noAF	Pathogenic	0.18
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.91	D
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.87	D
MetaSVM	Uncertain	-0.035	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		3.4
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-7.8	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0030	D
Polyphen		1.0	D
Vest4		0.62
MutPred		0.70		Gain of glycosylation at T181 (P = 0.0646)
MVP		0.68
MPC		0.41
ClinPred		1.0	D
GERP RS		4.7
Varity_R		0.77
gMVP		0.47
Mutation Taster		=60/40	polymorphism

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

Other links and lift over

dbSNP: rs200688205; hg19: chr3-151463403;