Variant 11-67646860-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_080658.2(ACY3):c.184C>T(p.Arg62Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000136 in 1,612,582 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000089 ( 0 hom. )

Consequence

ACY3
NM_080658.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0220

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:

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ACMG classification

Classification made for transcript

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 linkuse as main transcript	c.184C>T	p.Arg62Cys	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.184C>T	p.Arg62Cys	missense_variant	3/8	1	NM_080658.2	P1
ACY3	ENST00000529256.1 linkuse as main transcript	c.-180C>T		5_prime_UTR_variant	2/7	3

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000490

AC:

AN:

244882

Hom.:

AF XY:

0.0000598

AC XY:

AN XY:

133770

show subpopulations

Gnomad AFR exome

AF:

0.000326

Gnomad AMR exome

AF:

0.0000583

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0000655

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000913

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000890

AC:

AN:

1460322

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

726508

show subpopulations

Gnomad4 AFR exome

AF:

0.0000897

Gnomad4 AMR exome

AF:

0.0000895

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000403

AC XY:

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000831

ExAC

AF:

0.0000579

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

Mar 07, 2024

The c.184C>T (p.R62C) alteration is located in exon 3 (coding exon 1) of the ACY3 gene. This alteration results from a C to T substitution at nucleotide position 184, causing the arginine (R) at amino acid position 62 to be replaced by a cysteine (C). 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

0.097

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Uncertain

0.74

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.54

M_CAP

Pathogenic

0.55

MetaRNN

Uncertain

0.49

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.87

D;D

PrimateAI

Benign

0.40

PROVEAN

Uncertain

-3.6

REVEL

Uncertain

0.30

Sift

Benign

0.14

Sift4G

Benign

0.078

Polyphen

0.028

Vest4

0.18

MutPred

0.59

Loss of disorder (P = 0.0637);

MVP

0.84

MPC

0.18

ClinPred

0.044

GERP RS

0.48

Varity_R

0.14

gMVP

0.52

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