Variant 11-67644822-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_080658.2(ACY3):c.682G>A(p.Val228Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000393 in 1,579,238 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000039 ( 0 hom. )

Consequence

ACY3
NM_080658.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -2.17

Variant links:

Genes affected

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

ACY3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.065769136).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACY3	NM_080658.2 linkuse as main transcript	c.682G>A	p.Val228Ile	missense_variant	7/8	ENST00000255082.8	NP_542389.1	Q96HD9A0A024R5L2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACY3	ENST00000255082.8 linkuse as main transcript	c.682G>A	p.Val228Ile	missense_variant	7/8	1	NM_080658.2	ENSP00000255082.3		Q96HD9
ACY3	ENST00000529256.1 linkuse as main transcript	c.319G>A	p.Val107Ile	missense_variant	6/7	3		ENSP00000434270.1		E9PRA7

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152142

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000513

AC:

AN:

195066

Hom.:

AF XY:

0.0000476

AC XY:

AN XY:

105126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000426

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000481

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000392

AC:

AN:

1426978

Hom.:

Cov.:

AF XY:

0.0000396

AC XY:

AN XY:

707068

show subpopulations

Gnomad4 AFR exome

AF:

0.0000613

Gnomad4 AMR exome

AF:

0.0000258

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000133

Gnomad4 SAS exome

AF:

0.0000242

Gnomad4 FIN exome

AF:

0.0000198

Gnomad4 NFE exome

AF:

0.0000393

Gnomad4 OTH exome

AF:

0.0000338

GnomAD4 genome

AF:

0.0000394

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000152

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 09, 2023

The c.682G>A (p.V228I) alteration is located in exon 7 (coding exon 5) of the ACY3 gene. This alteration results from a G to A substitution at nucleotide position 682, causing the valine (V) at amino acid position 228 to be replaced by an isoleucine (I). 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

0.075

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.36

CADD

Benign

0.024

DANN

Benign

0.79

DEOGEN2

Uncertain

0.47

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.8

FATHMM_MKL

Benign

0.00077

LIST_S2

Benign

0.092

T;T

M_CAP

Benign

0.024

MetaRNN

Benign

0.066

T;T

MetaSVM

Uncertain

0.058

MutationAssessor

Benign

1.0

L;.

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.55

N;N

REVEL

Benign

0.17

Sift

Benign

0.064

T;T

Sift4G

Benign

0.17

T;T

Polyphen

0.0

B;.

Vest4

0.15

MVP

0.45

MPC

0.10

ClinPred

0.026

GERP RS

-6.8

Varity_R

0.027

gMVP

0.42

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over