chr3-151745519-G-A

Position:

• chr3-151745519-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_207365.4(AADACL2):​c.442G>A​(p.Ala148Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000496 in 1,612,224 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000085 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000046 (0 hom.)
• Consequence: AADACL2 NM_207365.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.10

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1750918).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AADACL2	NM_207365.4	c.442G>A	p.Ala148Thr	missense_variant	4/5	ENST00000356517.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AADACL2	ENST00000356517.4	c.442G>A	p.Ala148Thr	missense_variant	4/5	1	NM_207365.4	P1
AADACL2	ENST00000445270.1	c.*57G>A		3_prime_UTR_variant, NMD_transcript_variant	3/4	1

Frequencies

GnomAD3 genomes AF: 0.0000855 AC: 13 AN: 152064 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000483

Gnomad AMI AF: 0.00659

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000160 AC: 4 AN: 249240 Hom.: 0 AF XY: 0.0000223 AC XY: 3 AN XY: 134658

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: 0.0000354

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000459 AC: 67 AN: 1460160 Hom.: 0 Cov.: 29 AF XY: 0.0000413 AC XY: 30 AN XY: 726260

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000594

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome AF: 0.0000855 AC: 13 AN: 152064 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74278

Gnomad4 AFR AF: 0.0000483

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000330 Hom.: 0

ExAC AF: 0.0000412 AC: 5

EpiCase AF: 0.0000547

EpiControl AF: 0.0000595

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.41
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.88	D
M_CAP	Benign	0.0058	T
MetaRNN	Benign	0.18	T
MetaSVM	Benign	-0.72	T
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.36	T
PROVEAN	Uncertain	-2.4	N
REVEL	Benign	0.28
Sift	Benign	0.058	T
Sift4G	Benign	0.092	T
Polyphen		0.98	D
Vest4		0.24
MVP		0.13
MPC		0.12
ClinPred		0.66	D
GERP RS		2.8
Varity_R		0.13
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs756826800; hg19: chr3-151463307;