Variant 1-1472082-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_031921.6(ATAD3B):c.198G>C(p.Glu66Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00015 in 139,672 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. E66G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00015 ( 0 hom., cov: 25)

Exomes 𝑓: 0.00014 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATAD3B
NM_031921.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.88

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]

ATAD3B links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.17635229).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD3B	NM_031921.6 linkuse as main transcript	c.198G>C	p.Glu66Asp	missense_variant	1/16	ENST00000673477.1	NP_114127.3	Q5T9A4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATAD3B	ENST00000673477.1 linkuse as main transcript	c.198G>C	p.Glu66Asp	missense_variant	1/16		NM_031921.6	ENSP00000500094.1		Q5T9A4-1
ATAD3B	ENST00000308647.8 linkuse as main transcript	c.198G>C	p.Glu66Asp	missense_variant	1/14	1		ENSP00000311766.8		A0A5K1VW56

Frequencies

GnomAD3 genomes

AF:

0.000150

AC:

AN:

139602

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000286

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000141

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:

0.000256

Gnomad OTH

AF:

0.000515

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000141

AC:

149

AN:

1056220

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

500564

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000298

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000810

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000156

Gnomad4 OTH exome

AF:

0.000122

GnomAD4 genome

AF:

0.000150

AC:

AN:

139672

Hom.:

Cov.:

AF XY:

0.000118

AC XY:

AN XY:

67870

show subpopulations

Gnomad4 AFR

AF:

0.0000286

Gnomad4 AMR

AF:

0.000141

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000256

Gnomad4 OTH

AF:

0.000511

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 submitter

clinical testing

Ambry Genetics

Apr 11, 2023

The c.198G>C (p.E66D) alteration is located in exon 1 (coding exon 1) of the ATAD3B gene. This alteration results from a G to C substitution at nucleotide position 198, causing the glutamic acid (E) at amino acid position 66 to be replaced by an aspartic acid (D). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.14

BayesDel_noAF

Benign

-0.44

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0085

Eigen

Benign

-0.57

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.84

M_CAP

Pathogenic

0.90

MetaRNN

Benign

0.18

MetaSVM

Benign

-0.75

MutationAssessor

Benign

-0.33

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-1.6

REVEL

Uncertain

0.31

Sift

Benign

0.51

Sift4G

Benign

0.53

Polyphen

0.017

Vest4

0.071

MutPred

0.24

Loss of helix (P = 0.0017);

MVP

0.67

MPC

0.88

ClinPred

0.68

GERP RS

2.6

Varity_R

0.16

gMVP

0.068

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over