chr3-151757515-T-C

Position:

• chr3-151757515-T-C

Variant summary

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

The NM_207365.4(AADACL2):​c.1127T>C​(p.Phe376Ser) 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. 12/21 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 NM_207365.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.27

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.818

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AADACL2	NM_207365.4	c.1127T>C	p.Phe376Ser	missense_variant	5/5	ENST00000356517.4	NP_997248.2
AADACL2-AS1	NR_110203.1	n.380-6004A>G		intron_variant, non_coding_transcript_variant
AADACL2-AS1	NR_110202.1	n.380-2384A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AADACL2	ENST00000356517.4	c.1127T>C	p.Phe376Ser	missense_variant	5/5	1	NM_207365.4	ENSP00000348911	P1
AADACL2	ENST00000445270.1	c.*742T>C		3_prime_UTR_variant, NMD_transcript_variant	4/4	1		ENSP00000387390
AADACL2-AS1	ENST00000483843.6	n.500-2384A>G		intron_variant, non_coding_transcript_variant		5
AADACL2-AS1	ENST00000475855.1	n.380-2384A>G		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

Dec 09, 2023

The c.1127T>C (p.F376S) alteration is located in exon 5 (coding exon 5) of the AADACL2 gene. This alteration results from a T to C substitution at nucleotide position 1127, causing the phenylalanine (F) at amino acid position 376 to be replaced by a serine (S). 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	Uncertain	0.47
BayesDel_addAF	Benign	-0.026	T
BayesDel_noAF	Benign	-0.28
CADD	Benign	15
DANN	Benign	0.96
DEOGEN2	Benign	0.29	T
Eigen	Benign	-0.76
Eigen_PC	Benign	-0.97
FATHMM_MKL	Benign	0.39	N
M_CAP	Benign	0.0060	T
MetaRNN	Pathogenic	0.82	D
MetaSVM	Benign	-0.66	T
MutationAssessor	Uncertain	2.5	M
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.3	D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0010	D
Polyphen		0.82	P
Vest4		0.41
MutPred		0.80		Gain of disorder (P = 0.0032);
MVP		0.15
MPC		0.15
ClinPred		0.99	D
GERP RS		-4.4
Varity_R		0.17
gMVP		0.55

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: chr3-151475303;