11-67642836-A-G

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong

The ENST00000255082.8(ACY3):ā€‹c.848T>Cā€‹(p.Ile283Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000547 in 1,461,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000055 ( 0 hom. )

Consequence

ACY3
ENST00000255082.8 missense

Scores

10
7
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.87
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.965

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ACY3NM_080658.2 linkuse as main transcriptc.848T>C p.Ile283Thr missense_variant 8/8 ENST00000255082.8 NP_542389.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ACY3ENST00000255082.8 linkuse as main transcriptc.848T>C p.Ile283Thr missense_variant 8/81 NM_080658.2 ENSP00000255082 P1
ACY3ENST00000529256.1 linkuse as main transcriptc.485T>C p.Ile162Thr missense_variant 7/73 ENSP00000434270

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251288
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135900
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000547
AC:
8
AN:
1461820
Hom.:
0
Cov.:
31
AF XY:
0.00000688
AC XY:
5
AN XY:
727206
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33
Bravo
AF:
0.00000378
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsMay 08, 2024The c.848T>C (p.I283T) alteration is located in exon 8 (coding exon 6) of the ACY3 gene. This alteration results from a T to C substitution at nucleotide position 848, causing the isoleucine (I) at amino acid position 283 to be replaced by a threonine (T). 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
Pathogenic
0.79
BayesDel_addAF
Pathogenic
0.27
D
BayesDel_noAF
Pathogenic
0.33
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Pathogenic
0.83
D;D
Eigen
Uncertain
0.58
Eigen_PC
Uncertain
0.41
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.78
T;T
M_CAP
Pathogenic
0.45
D
MetaRNN
Pathogenic
0.96
D;D
MetaSVM
Pathogenic
1.1
D
MutationAssessor
Pathogenic
3.3
M;.
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.56
T
PROVEAN
Uncertain
-4.3
D;D
REVEL
Pathogenic
0.89
Sift
Uncertain
0.0020
D;D
Sift4G
Uncertain
0.0040
D;D
Polyphen
0.99
D;.
Vest4
0.78
MutPred
0.80
Loss of stability (P = 0.0476);.;
MVP
0.98
MPC
0.65
ClinPred
0.96
D
GERP RS
4.4
Varity_R
0.45
gMVP
0.91

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.

Other links and lift over

dbSNP: rs764559224; hg19: chr11-67410307; API