3-151734070-G-T

Position:

• chr3-151734070-G-T

Variant summary

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

The NM_207365.4(AADACL2):​c.35G>T​(p.Cys12Phe) 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. 14/21 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)
• Consequence: AADACL2 NM_207365.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.847

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=0.15886137).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AADACL2	NM_207365.4	c.35G>T	p.Cys12Phe	missense_variant	1/5	ENST00000356517.4	NP_997248.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AADACL2	ENST00000356517.4	c.35G>T	p.Cys12Phe	missense_variant	1/5	1	NM_207365.4	ENSP00000348911.3
AADACL2	ENST00000445270.1	n.35G>T		non_coding_transcript_exon_variant	1/4	1		ENSP00000387390.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

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

Nov 10, 2024

The c.35G>T (p.C12F) alteration is located in exon 1 (coding exon 1) of the AADACL2 gene. This alteration results from a G to T substitution at nucleotide position 35, causing the cysteine (C) at amino acid position 12 to be replaced by a phenylalanine (F). 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	0.073
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	13
DANN	Benign	0.83
DEOGEN2	Benign	0.13	T
Eigen	Benign	-0.97
Eigen_PC	Benign	-0.89
FATHMM_MKL	Benign	0.25	N
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.8	L
PrimateAI	Benign	0.47	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.053
Sift	Benign	0.38	T
Sift4G	Benign	0.76	T
Polyphen		0.020	B
Vest4		0.34
MutPred		0.44		Loss of helix (P = 0.0017);
MVP		0.055
MPC		0.094
ClinPred		0.067	T
GERP RS		2.2
Varity_R		0.094
gMVP		0.25

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: chr3-151451858;