Variant 11-67647021-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_080658.2(ACY3):c.23G>A(p.Arg8Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.809 in 1,541,728 control chromosomes in the GnomAD database, including 511,217 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R8W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.72 ( 42405 hom., cov: 33)

Exomes 𝑓: 0.82 ( 468812 hom. )

Consequence

ACY3
NM_080658.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0660

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 Benign. Variant got -8 ACMG points.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.896 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACY3	NM_080658.2 linkuse as main transcript	c.23G>A	p.Arg8Gln	missense_variant	3/8	ENST00000255082.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACY3	ENST00000255082.8 linkuse as main transcript	c.23G>A	p.Arg8Gln	missense_variant	3/8	1	NM_080658.2	P1
ACY3	ENST00000529256.1 linkuse as main transcript	c.-245-96G>A		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.725

AC:

110190

AN:

152030

Hom.:

42391

Cov.:

show subpopulations

Gnomad AFR

AF:

0.442

Gnomad AMI

AF:

0.771

Gnomad AMR

AF:

0.806

Gnomad ASJ

AF:

0.863

Gnomad EAS

AF:

0.765

Gnomad SAS

AF:

0.918

Gnomad FIN

AF:

0.906

Gnomad MID

AF:

0.810

Gnomad NFE

AF:

0.825

Gnomad OTH

AF:

0.738

GnomAD3 exomes

AF:

0.829

AC:

127240

AN:

153444

Hom.:

53626

AF XY:

0.839

AC XY:

68891

AN XY:

82074

show subpopulations

Gnomad AFR exome

AF:

0.434

Gnomad AMR exome

AF:

0.870

Gnomad ASJ exome

AF:

0.866

Gnomad EAS exome

AF:

0.783

Gnomad SAS exome

AF:

0.921

Gnomad FIN exome

AF:

0.899

Gnomad NFE exome

AF:

0.821

Gnomad OTH exome

AF:

0.826

GnomAD4 exome

AF:

0.818

AC:

1137155

AN:

1389580

Hom.:

468812

Cov.:

AF XY:

0.822

AC XY:

562306

AN XY:

683782

show subpopulations

Gnomad4 AFR exome

AF:

0.430

Gnomad4 AMR exome

AF:

0.864

Gnomad4 ASJ exome

AF:

0.863

Gnomad4 EAS exome

AF:

0.753

Gnomad4 SAS exome

AF:

0.922

Gnomad4 FIN exome

AF:

0.893

Gnomad4 NFE exome

AF:

0.819

Gnomad4 OTH exome

AF:

0.801

GnomAD4 genome

AF:

0.725

AC:

110244

AN:

152148

Hom.:

42405

Cov.:

AF XY:

0.732

AC XY:

54483

AN XY:

74396

show subpopulations

Gnomad4 AFR

AF:

0.442

Gnomad4 AMR

AF:

0.807

Gnomad4 ASJ

AF:

0.863

Gnomad4 EAS

AF:

0.766

Gnomad4 SAS

AF:

0.919

Gnomad4 FIN

AF:

0.906

Gnomad4 NFE

AF:

0.825

Gnomad4 OTH

AF:

0.740

Alfa

AF:

0.815

Hom.:

89165

Bravo

AF:

0.705

TwinsUK

AF:

0.824

AC:

3054

ALSPAC

AF:

0.827

AC:

3189

ESP6500AA

AF:

0.489

AC:

2099

ESP6500EA

AF:

0.828

AC:

6979

ExAC

AF:

0.768

AC:

77630

Asia WGS

AF:

0.790

AC:

2744

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.018

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.57

MetaRNN

Benign

5.9e-7

MetaSVM

Benign

-0.94

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.43

PROVEAN

Benign

-0.060

REVEL

Benign

0.17

Sift

Benign

0.30

Sift4G

Benign

0.48

Polyphen

0.052

Vest4

0.030

MPC

0.15

ClinPred

0.011

GERP RS

1.0

Varity_R

0.076

gMVP

0.24

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.97

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.97

Position offset: -2

DS_AL_spliceai

0.53

Position offset: 42

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over