3-151740853-T-C

Position:

• chr3-151740853-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_207365.4(AADACL2):​c.346T>C​(p.Cys116Arg) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: AADACL2 NM_207365.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.19

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 Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.954

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AADACL2	NM_207365.4	c.346T>C	p.Cys116Arg	missense_variant	2/5	ENST00000356517.4	NP_997248.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AADACL2	ENST00000356517.4	c.346T>C	p.Cys116Arg	missense_variant	2/5	1	NM_207365.4	ENSP00000348911	P1
AADACL2	ENST00000445270.1	c.139-3240T>C		intron_variant, NMD_transcript_variant		1		ENSP00000387390

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Aug 02, 2023

The c.346T>C (p.C116R) alteration is located in exon 2 (coding exon 2) of the AADACL2 gene. This alteration results from a T to C substitution at nucleotide position 346, causing the cysteine (C) at amino acid position 116 to be replaced by an arginine (R). 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	Pathogenic	0.62
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T
Eigen	Benign	0.0036
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.55	D
M_CAP	Benign	0.0022	T
MetaRNN	Pathogenic	0.95	D
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.77	N
MutationTaster	Benign	0.99	D
PrimateAI	Uncertain	0.56	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Benign	0.23
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.034	D
Polyphen		0.97	D
Vest4		0.72
MutPred		0.84		Gain of MoRF binding (P = 0.0025);
MVP		0.20
MPC		0.20
ClinPred		0.98	D
GERP RS		-3.5
Varity_R		0.89
gMVP		0.57

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: chr3-151458641;