Variant 1-1472081-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_031921.6(ATAD3B):c.197A>G(p.Glu66Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000236 in 1,167,170 control chromosomes in the GnomAD database, including 2 homozygotes. 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. E66D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 24)

Exomes 𝑓: 0.00023 ( 2 hom. )

Consequence

ATAD3B
NM_031921.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.29

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.35011405).

BS2

High Homozygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD3B	NM_031921.6 linkuse as main transcript	c.197A>G	p.Glu66Gly	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.197A>G	p.Glu66Gly	missense_variant	1/16		NM_031921.6	ENSP00000500094.1		Q5T9A4-1
ATAD3B	ENST00000308647.8 linkuse as main transcript	c.197A>G	p.Glu66Gly	missense_variant	1/14	1		ENSP00000311766.8		A0A5K1VW56

Frequencies

GnomAD3 genomes

AF:

0.000271

AC:

AN:

136680

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000298

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00221

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000243

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000462

AC:

AN:

4332

Hom.:

AF XY:

0.000848

AC XY:

AN XY:

2358

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000585

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000231

AC:

238

AN:

1030490

Hom.:

Cov.:

AF XY:

0.000248

AC XY:

121

AN XY:

487450

show subpopulations

Gnomad4 AFR exome

AF:

0.0000514

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00304

Gnomad4 NFE exome

AF:

0.000175

Gnomad4 OTH exome

AF:

0.000128

GnomAD4 genome

AF:

0.000271

AC:

AN:

136680

Hom.:

Cov.:

AF XY:

0.000332

AC XY:

AN XY:

66184

show subpopulations

Gnomad4 AFR

AF:

0.0000298

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00221

Gnomad4 NFE

AF:

0.000243

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000270

Hom.:

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

Aug 17, 2022

The c.197A>G (p.E66G) 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 197, causing the glutamic acid (E) at amino acid position 66 to be replaced by a glycine (G). 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

0.52

BayesDel_addAF

Uncertain

0.029

BayesDel_noAF

Benign

-0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

Eigen

Uncertain

0.40

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.91

M_CAP

Pathogenic

0.97

MetaRNN

Benign

0.35

MetaSVM

Uncertain

0.35

MutationAssessor

Benign

2.0

PrimateAI

Pathogenic

0.88

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.57

Sift

Uncertain

0.011

Sift4G

Uncertain

0.056

Polyphen

0.93

Vest4

0.15

MutPred

0.31

Loss of helix (P = 3e-04);

MVP

0.85

MPC

2.1

ClinPred

0.46

GERP RS

2.6

Varity_R

0.50

gMVP

0.097

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