1-12725412-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.640C>T​(p.Arg214Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

AADACL3
NM_001103170.3 missense

Scores

5
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.879
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=0.08095229).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
AADACL3NM_001103170.3 linkc.640C>T p.Arg214Trp missense_variant Exon 4 of 4 ENST00000359318.8 NP_001096640.2 Q5VUY0
AADACL3NR_111984.2 linkn.490C>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.640C>T p.Arg214Trp missense_variant Exon 4 of 4 3 NM_001103170.3 ENSP00000352268.6 Q5VUY0
AADACL3ENST00000620146.2 linkn.485C>T non_coding_transcript_exon_variant Exon 3 of 3 2

Frequencies

GnomAD3 genomes
AF:
0.0000592
AC:
9
AN:
152128
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000145
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000192
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000482
AC:
12
AN:
249060
Hom.:
0
AF XY:
0.0000296
AC XY:
4
AN XY:
135106
show subpopulations
Gnomad AFR exome
AF:
0.0000646
Gnomad AMR exome
AF:
0.0000870
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000556
Gnomad SAS exome
AF:
0.0000654
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000354
Gnomad OTH exome
AF:
0.000165
GnomAD4 exome
AF:
0.0000267
AC:
39
AN:
1461740
Hom.:
0
Cov.:
31
AF XY:
0.0000234
AC XY:
17
AN XY:
727158
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.0000580
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000189
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.0000591
AC:
9
AN:
152246
Hom.:
0
Cov.:
32
AF XY:
0.0000940
AC XY:
7
AN XY:
74442
show subpopulations
Gnomad4 AFR
AF:
0.000144
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000393
Hom.:
0
Bravo
AF:
0.0000604
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000259
AC:
1
ESP6500AA
AF:
0.000264
AC:
1
ESP6500EA
AF:
0.000244
AC:
2
ExAC
AF:
0.0000579
AC:
7

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 30, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.469C>T (p.R157W) 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 469, causing the arginine (R) at amino acid position 157 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
0.14
BayesDel_addAF
Benign
-0.31
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
22
DANN
Uncertain
1.0
Eigen
Uncertain
0.19
Eigen_PC
Benign
0.010
FATHMM_MKL
Uncertain
0.84
D
LIST_S2
Uncertain
0.93
D
M_CAP
Benign
0.021
T
MetaRNN
Benign
0.081
T
MetaSVM
Benign
-1.1
T
PrimateAI
Benign
0.28
T
REVEL
Benign
0.092
Sift4G
Uncertain
0.0020
D
Vest4
0.18
MVP
0.095
MPC
0.54
ClinPred
0.49
T
GERP RS
1.9
Varity_R
0.10
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.

Other links and lift over

dbSNP: rs143650139; hg19: chr1-12785379; API