1-1471931-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031921.6(ATAD3B):​c.47C>T​(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 151,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

ATAD3B
NM_031921.6 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.546

Publications

0 publications found
Variant links:
Genes affected
ATAD3B (HGNC:24007): (ATPase family AAA domain containing 3B) The protein encoded by this gene is localized to the mitochondrial inner membrane, where it can bind to a highly-related protein, ATAD3A. ATAD3A appears to interact with matrix nucleoid complexes, and the encoded protein negatively regulates that interaction. This gene is expressed almost exclusively in pluripotent embryonic stem cells and some cancer cells. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.22216234).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATAD3BNM_031921.6 linkc.47C>T p.Ala16Val missense_variant Exon 1 of 16 ENST00000673477.1 NP_114127.3 Q5T9A4-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATAD3BENST00000673477.1 linkc.47C>T p.Ala16Val missense_variant Exon 1 of 16 NM_031921.6 ENSP00000500094.1 Q5T9A4-1
ATAD3BENST00000308647.8 linkc.47C>T p.Ala16Val missense_variant Exon 1 of 14 1 ENSP00000311766.8 A0A5K1VW56

Frequencies

GnomAD3 genomes
AF:
0.00000662
AC:
1
AN:
151018
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000659
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
GnomAD4 exome
Data not reliable, filtered out with message: AC0;AS_VQSR
AF:
0.00
AC:
0
AN:
1092562
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
517342
African (AFR)
AF:
0.00
AC:
0
AN:
22636
American (AMR)
AF:
0.00
AC:
0
AN:
8538
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
14052
East Asian (EAS)
AF:
0.00
AC:
0
AN:
25868
South Asian (SAS)
AF:
0.00
AC:
0
AN:
20242
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
33242
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2888
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
921700
Other (OTH)
AF:
0.00
AC:
0
AN:
43396
GnomAD4 genome
AF:
0.00000662
AC:
1
AN:
151018
Hom.:
0
Cov.:
30
AF XY:
0.0000136
AC XY:
1
AN XY:
73752
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41060
American (AMR)
AF:
0.0000659
AC:
1
AN:
15176
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3466
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5096
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4794
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10470
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67668
Other (OTH)
AF:
0.00
AC:
0
AN:
2066
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
0.00
Hom.:
0

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 03, 2023
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing

The c.47C>T (p.A16V) alteration is located in exon 1 (coding exon 1) of the ATAD3B gene. This alteration results from a C to T substitution at nucleotide position 47, causing the alanine (A) at amino acid position 16 to be replaced by a valine (V). 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
0.093
BayesDel_addAF
Benign
-0.061
T
BayesDel_noAF
Benign
-0.33
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.017
T
Eigen
Benign
-0.61
Eigen_PC
Benign
-0.62
FATHMM_MKL
Benign
0.14
N
LIST_S2
Benign
0.57
T
M_CAP
Pathogenic
0.87
D
MetaRNN
Benign
0.22
T
MetaSVM
Benign
-0.66
T
MutationAssessor
Benign
1.1
L
PhyloP100
0.55
PrimateAI
Pathogenic
0.80
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.20
Sift
Benign
0.23
T
Sift4G
Uncertain
0.024
D
Polyphen
0.52
P
Vest4
0.084
MutPred
0.16
Loss of glycosylation at P18 (P = 0.1241);
MVP
0.66
MPC
0.85
ClinPred
0.21
T
GERP RS
2.6
PromoterAI
0.033
Neutral
Varity_R
0.045
gMVP
0.060
Mutation Taster
=92/8
polymorphism

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

Other links and lift over

dbSNP: rs948002957; hg19: chr1-1407311; API