Genetic Variant ACY3:p.Arg8Gln (chr11-67647021-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 2P and 8B. PP3_ModerateBA1

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. 14/25 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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

Publications

35 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

PP3

Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

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 rank	MANE	Protein	UniProt
ACY3	NM_080658.2 link	c.23G>A	p.Arg8Gln	missense_variant	Exon 3 of 8	ENST00000255082.8	NP_542389.1	Q96HD9A0A024R5L2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACY3	ENST00000255082.8 link	c.23G>A	p.Arg8Gln	missense_variant	Exon 3 of 8	1	NM_080658.2	ENSP00000255082.3		Q96HD9
ACY3	ENST00000529256.1 link	c.-245-96G>A		intron_variant	Intron 1 of 6	3		ENSP00000434270.1		E9PRA7

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

GnomAD2 exomes

AF:

0.829

AC:

127240

AN:

153444

AF XY:

0.839

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 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

African (AFR)

AF:

0.430

AC:

13595

AN:

31636

American (AMR)

AF:

0.864

AC:

30363

AN:

35156

Ashkenazi Jewish (ASJ)

AF:

0.863

AC:

21317

AN:

24702

East Asian (EAS)

AF:

0.753

AC:

27009

AN:

35862

South Asian (SAS)

AF:

0.922

AC:

72946

AN:

79104

European-Finnish (FIN)

AF:

0.893

AC:

42004

AN:

47058

Middle Eastern (MID)

AF:

0.821

AC:

4544

AN:

5534

European-Non Finnish (NFE)

AF:

0.819

AC:

879358

AN:

1073058

Other (OTH)

AF:

0.801

AC:

46019

AN:

57470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

11065

22130

33194

44259

55324

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20536

41072

61608

82144

102680

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.725

AC:

110244

AN:

152148

Hom.:

42405

Cov.:

AF XY:

0.732

AC XY:

54483

AN XY:

74396

show subpopulations

African (AFR)

AF:

0.442

AC:

18349

AN:

41492

American (AMR)

AF:

0.807

AC:

12337

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.863

AC:

2994

AN:

3470

East Asian (EAS)

AF:

0.766

AC:

3949

AN:

5156

South Asian (SAS)

AF:

0.919

AC:

4436

AN:

4828

European-Finnish (FIN)

AF:

0.906

AC:

9610

AN:

10606

Middle Eastern (MID)

AF:

0.799

AC:

235

AN:

294

European-Non Finnish (NFE)

AF:

0.825

AC:

56070

AN:

67986

Other (OTH)

AF:

0.740

AC:

1562

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1359

2718

4078

5437

6796

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

818

1636

2454

3272

4090

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.811

Hom.:

131255

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

(source)

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

PhyloP100

-0.066

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

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over