11-67645856-C-T

Variant summary

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

The NM_080658.2(ACY3):c.268G>A(p.Val90Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACY3 NM_080658.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.581

Genes affected

ACY3 (HGNC:24104): (aminoacylase 3) Predicted to enable aminoacylase activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACY3	NM_080658.2	c.268G>A	p.Val90Met	missense_variant	4/8	ENST00000255082.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACY3	ENST00000255082.8	c.268G>A	p.Val90Met	missense_variant	4/8	1	NM_080658.2	P1
ACY3	ENST00000529256.1	c.-96G>A		5_prime_UTR_variant	3/7	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 32

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

Sep 29, 2022

The c.268G>A (p.V90M) alteration is located in exon 4 (coding exon 2) of the ACY3 gene. This alteration results from a G to A substitution at nucleotide position 268, causing the valine (V) at amino acid position 90 to be replaced by a methionine (M). 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	0.20
BayesDel_addAF	Uncertain	0.037	T
BayesDel_noAF	Benign	-0.19
Cadd	Benign	18
Dann	Uncertain	1.0
DEOGEN2	Benign	0.41	T
Eigen	Benign	0.086
Eigen_PC	Benign	-0.041
FATHMM_MKL	Benign	0.39	N
LIST_S2	Benign	0.74	T
M_CAP	Uncertain	0.13	D
MetaRNN	Uncertain	0.73	D
MetaSVM	Pathogenic	0.85	D
MutationAssessor	Uncertain	2.2	M
MutationTaster	Benign	1.0	D;N
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.45
Sift	Benign	0.037	D
Sift4G	Benign	0.067	T
Polyphen		1.0	D
Vest4		0.49
MutPred		0.60		Gain of catalytic residue at V90 (P = 0.0457);
MVP		0.85
MPC		0.25
ClinPred		0.80	D
GERP RS		3.0
Varity_R		0.099
gMVP		0.28

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: chr11-67413327;