NM_031921.6:c.200A>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_031921.6(ATAD3B):​c.200A>G​(p.His67Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000172 in 1,165,404 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000075 ( 0 hom., cov: 24)
Exomes 𝑓: 9.7e-7 ( 0 hom. )

Consequence

ATAD3B
NM_031921.6 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.04
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.03328821).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATAD3BNM_031921.6 linkc.200A>G p.His67Arg 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.200A>G p.His67Arg missense_variant Exon 1 of 16 NM_031921.6 ENSP00000500094.1 Q5T9A4-1
ATAD3BENST00000308647.8 linkc.200A>G p.His67Arg missense_variant Exon 1 of 14 1 ENSP00000311766.8 A0A5K1VW56

Frequencies

GnomAD3 genomes
AF:
0.00000749
AC:
1
AN:
133560
Hom.:
0
Cov.:
24
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000751
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
AF:
9.69e-7
AC:
1
AN:
1031844
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
489110
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000666
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000749
AC:
1
AN:
133560
Hom.:
0
Cov.:
24
AF XY:
0.0000155
AC XY:
1
AN XY:
64504
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000751
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

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 21, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.200A>G (p.H67R) alteration is located in exon 1 (coding exon 1) of the ATAD3B gene. This alteration results from a A to G substitution at nucleotide position 200, causing the histidine (H) at amino acid position 67 to be replaced by an arginine (R). 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
0.094
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.71
CADD
Benign
21
DANN
Benign
0.74
DEOGEN2
Benign
0.0048
T
Eigen
Benign
-0.62
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.75
D
LIST_S2
Uncertain
0.91
D
M_CAP
Uncertain
0.14
D
MetaRNN
Benign
0.033
T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
-0.42
N
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
0.64
N
REVEL
Benign
0.036
Sift
Benign
0.73
T
Sift4G
Benign
0.60
T
Polyphen
0.0030
B
Vest4
0.18
MutPred
0.21
Gain of MoRF binding (P = 0.012);
MVP
0.36
MPC
1.0
ClinPred
0.11
T
GERP RS
2.6
Varity_R
0.064
gMVP
0.023

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: rs1639353517; hg19: chr1-1407464; API