NM_207365.4:c.590C>T

Variant names:

• chr3-151745667-C-T
• rs760055575
• NM_207365.4:c.590C>T

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_207365.4(AADACL2):​c.590C>T​(p.Ala197Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000011 in 1,457,036 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: AADACL2 NM_207365.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.20

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AADACL2	NM_207365.4	c.590C>T	p.Ala197Val	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.590C>T	p.Ala197Val	missense_variant	Exon 4 of 5	1	NM_207365.4	ENSP00000348911.3
AADACL2	ENST00000445270.1	n.*205C>T		non_coding_transcript_exon_variant	Exon 3 of 4	1		ENSP00000387390.1
AADACL2	ENST00000445270.1	n.*205C>T		3_prime_UTR_variant	Exon 3 of 4	1		ENSP00000387390.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.0000122 AC: 3 AN: 245390 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 132850

Gnomad AFR exome AF: 0.00

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: 0.0000268

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000110 AC: 16 AN: 1457036 Hom.: 0 Cov.: 33 AF XY: 0.0000138 AC XY: 10 AN XY: 724598

Gnomad4 AFR exome AF: 0.0000303

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.0000353

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000901

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000301 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.28
FATHMM_MKL	Uncertain	0.83	D
M_CAP	Benign	0.0062	T
MetaRNN	Pathogenic	0.75	D
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	0.67	N
PrimateAI	Benign	0.38	T
PROVEAN	Uncertain	-2.5	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.094	T
Polyphen		1.0	D
Vest4		0.59
MutPred		0.67		Loss of disorder (P = 0.0803);
MVP		0.10
MPC		0.086
ClinPred		0.47	T
GERP RS		2.7
Varity_R		0.18
gMVP		0.37

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs760055575; hg19: chr3-151463455; COSMIC: COSV62929894;