11-67642783-A-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_080658.2(ACY3):c.901T>C(p.Phe301Leu) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: ACY3 NM_080658.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.213

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03963691).
• BP6: Variant 11-67642783-A-G is Benign according to our data. Variant chr11-67642783-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2278643.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACY3	NM_080658.2	c.901T>C	p.Phe301Leu	missense_variant	8/8	ENST00000255082.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACY3	ENST00000255082.8	c.901T>C	p.Phe301Leu	missense_variant	8/8	1	NM_080658.2	P1
ACY3	ENST00000529256.1	c.538T>C	p.Phe180Leu	missense_variant	7/7	3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 16, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Benign	-0.084	T
BayesDel_noAF	Benign	-0.36
Cadd	Benign	1.7
Dann	Benign	0.53
DEOGEN2	Benign	0.28	T;T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.21	T;T
M_CAP	Benign	0.039	D
MetaRNN	Benign	0.040	T;T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	-1.8	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Benign	1.1	N;N
REVEL	Benign	0.23
Sift	Benign	1.0	T;T
Sift4G	Benign	0.82	T;T
Polyphen		0.0	B;.
Vest4		0.015
MutPred		0.42		Loss of catalytic residue at F301 (P = 0.0047);.;
MVP		0.63
MPC		0.15
ClinPred		0.028	T
GERP RS		-2.0
Varity_R		0.039
gMVP		0.51

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: chr11-67410254;