chr1-12725418-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001103170.3(AADACL3):​c.646C>T​(p.Arg216Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,613,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R216Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

AADACL3
NM_001103170.3 missense

Scores

3
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.120
Variant links:
Genes affected
AADACL3 (HGNC:32037): (arylacetamide deacetylase like 3) Predicted to enable hydrolase activity. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1254119).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AADACL3NM_001103170.3 linkc.646C>T p.Arg216Trp missense_variant Exon 4 of 4 ENST00000359318.8 NP_001096640.2 Q5VUY0
AADACL3NR_111984.2 linkn.496C>T non_coding_transcript_exon_variant Exon 3 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
AADACL3ENST00000359318.8 linkc.646C>T p.Arg216Trp missense_variant Exon 4 of 4 3 NM_001103170.3 ENSP00000352268.6 Q5VUY0
AADACL3ENST00000620146.2 linkn.491C>T non_coding_transcript_exon_variant Exon 3 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152148
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000386
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:
0.0000281
AC:
7
AN:
248994
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135058
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000557
Gnomad SAS exome
AF:
0.0000655
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000266
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000185
AC:
27
AN:
1461702
Hom.:
0
Cov.:
31
AF XY:
0.0000206
AC XY:
15
AN XY:
727138
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000756
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000153
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152148
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74324
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000579
Hom.:
0
Bravo
AF:
0.0000453
ExAC
AF:
0.0000248
AC:
3
EpiCase
AF:
0.0000545
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Mar 12, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.475C>T (p.R159W) alteration is located in exon 4 (coding exon 3) of the AADACL3 gene. This alteration results from a C to T substitution at nucleotide position 475, causing the arginine (R) at amino acid position 159 to be replaced by a tryptophan (W). 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
0.21
BayesDel_addAF
Benign
-0.12
T
BayesDel_noAF
Benign
-0.23
CADD
Benign
20
DANN
Uncertain
1.0
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.50
FATHMM_MKL
Benign
0.058
N
LIST_S2
Uncertain
0.89
D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.13
T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.39
T
REVEL
Benign
0.098
Sift4G
Uncertain
0.0020
D
Vest4
0.18
MVP
0.040
MPC
0.56
ClinPred
0.70
D
GERP RS
1.1
Varity_R
0.12
gMVP
0.67

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: rs755539749; hg19: chr1-12785385; COSMIC: COSV60198164; API