3-151757506-C-T

Position:

• chr3-151757506-C-T

Variant summary

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

The ENST00000356517.4(AADACL2):​c.1118C>T​(p.Ala373Val) 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 benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: AADACL2 ENST00000356517.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.920

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

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=0.14425558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AADACL2	NM_207365.4	c.1118C>T	p.Ala373Val	missense_variant	5/5	ENST00000356517.4	NP_997248.2
AADACL2-AS1	NR_110203.1	n.380-5995G>A		intron_variant, non_coding_transcript_variant
AADACL2-AS1	NR_110202.1	n.380-2375G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AADACL2	ENST00000356517.4	c.1118C>T	p.Ala373Val	missense_variant	5/5	1	NM_207365.4	ENSP00000348911	P1
AADACL2	ENST00000445270.1	c.*733C>T		3_prime_UTR_variant, NMD_transcript_variant	4/4	1		ENSP00000387390
AADACL2-AS1	ENST00000483843.6	n.500-2375G>A		intron_variant, non_coding_transcript_variant		5
AADACL2-AS1	ENST00000475855.1	n.380-2375G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2022

The c.1118C>T (p.A373V) alteration is located in exon 5 (coding exon 5) of the AADACL2 gene. This alteration results from a C to T substitution at nucleotide position 1118, causing the alanine (A) at amino acid position 373 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.19
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Uncertain	0.98
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.16	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.28	T
PROVEAN	Uncertain	-2.8	D
REVEL	Benign	0.095
Sift	Benign	0.13	T
Sift4G	Benign	0.54	T
Polyphen		0.55	P
Vest4		0.15
MutPred		0.59		Loss of disorder (P = 0.1472);
MVP		0.014
MPC		0.27
ClinPred		0.75	D
GERP RS		3.2
Varity_R		0.063
gMVP		0.29

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-151475294;