Variant 1-1472044-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP3BS2

The NM_031921.6(ATAD3B):c.160G>T(p.Gly54Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00081 in 1,225,878 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00063 ( 2 hom., cov: 26)

Exomes 𝑓: 0.00083 ( 3 hom. )

Consequence

ATAD3B
NM_031921.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.88

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 -3 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.771

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD3B	NM_031921.6 linkuse as main transcript	c.160G>T	p.Gly54Cys	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.160G>T	p.Gly54Cys	missense_variant	1/16		NM_031921.6	ENSP00000500094.1		Q5T9A4-1
ATAD3B	ENST00000308647.8 linkuse as main transcript	c.160G>T	p.Gly54Cys	missense_variant	1/14	1		ENSP00000311766.8		A0A5K1VW56

Frequencies

GnomAD3 genomes

AF:

0.000631

AC:

AN:

147482

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000279

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000943

Gnomad ASJ

AF:

0.000290

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000101

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000937

Gnomad OTH

AF:

0.00147

GnomAD3 exomes

AF:

0.000152

AC:

AN:

6560

Hom.:

AF XY:

0.000297

AC XY:

AN XY:

3372

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:

0.00

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000835

AC:

900

AN:

1078292

Hom.:

Cov.:

AF XY:

0.000844

AC XY:

431

AN XY:

510406

show subpopulations

Gnomad4 AFR exome

AF:

0.000187

Gnomad4 AMR exome

AF:

0.000398

Gnomad4 ASJ exome

AF:

0.000297

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000312

Gnomad4 NFE exome

AF:

0.000940

Gnomad4 OTH exome

AF:

0.000543

GnomAD4 genome

AF:

0.000630

AC:

AN:

147586

Hom.:

Cov.:

AF XY:

0.000583

AC XY:

AN XY:

72026

show subpopulations

Gnomad4 AFR

AF:

0.000278

Gnomad4 AMR

AF:

0.000941

Gnomad4 ASJ

AF:

0.000290

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000101

Gnomad4 NFE

AF:

0.000937

Gnomad4 OTH

AF:

0.00146

Alfa

AF:

0.000594

Hom.:

Bravo

AF:

0.000574

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

Jul 09, 2021

The c.160G>T (p.G54C) alteration is located in exon 1 (coding exon 1) of the ATAD3B gene. This alteration results from a G to T substitution at nucleotide position 160, causing the glycine (G) at amino acid position 54 to be replaced by a cysteine (C). 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

Pathogenic

0.89

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.20

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.61

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.95

M_CAP

Pathogenic

0.97

MetaRNN

Pathogenic

0.77

MetaSVM

Pathogenic

0.94

MutationAssessor

Uncertain

2.8

PrimateAI

Pathogenic

0.96

PROVEAN

Uncertain

-2.9

REVEL

Pathogenic

0.81

Sift

Uncertain

0.0030

Sift4G

Uncertain

0.0050

Polyphen

1.0

Vest4

0.69

MVP

0.88

MPC

2.0

ClinPred

0.62

GERP RS

2.6

Varity_R

0.55

gMVP

0.20

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