Variant 1-1478686-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_031921.6(ATAD3B):c.325C>T(p.Arg109Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000104 in 1,541,860 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000034 ( 0 hom., cov: 26)

Exomes 𝑓: 0.0000079 ( 0 hom. )

Consequence

ATAD3B
NM_031921.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.29

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:

ATAD3B (HGNC:):

ATAD3B links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.787

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD3B	NM_031921.6 linkuse as main transcript	c.325C>T	p.Arg109Trp	missense_variant	3/16	ENST00000673477.1	NP_114127.3	Q5T9A4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
ATAD3B	ENST00000673477.1 linkuse as main transcript	c.325C>T	p.Arg109Trp	missense_variant	3/16		NM_031921.6	ENSP00000500094.1	Q5T9A4-1
ATAD3B	ENST00000308647.8 linkuse as main transcript	c.282+1336C>T		intron_variant		1		ENSP00000311766.8	A0A5K1VW56
ATAD3B	ENST00000472194.6 linkuse as main transcript	n.661C>T		non_coding_transcript_exon_variant	1/14	1

Frequencies

GnomAD3 genomes

AF:

0.0000340

AC:

AN:

147198

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000503

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000221

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000300

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000262

AC:

AN:

152896

Hom.:

AF XY:

0.0000370

AC XY:

AN XY:

80990

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000811

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000879

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000789

AC:

AN:

1394662

Hom.:

Cov.:

AF XY:

0.0000102

AC XY:

AN XY:

687572

show subpopulations

Gnomad4 AFR exome

AF:

0.0000636

Gnomad4 AMR exome

AF:

0.0000842

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000632

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.29e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000340

AC:

AN:

147198

Hom.:

Cov.:

AF XY:

0.0000559

AC XY:

AN XY:

71570

show subpopulations

Gnomad4 AFR

AF:

0.0000503

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000221

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000300

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

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

Jan 26, 2022

The c.325C>T (p.R109W) alteration is located in exon 3 (coding exon 3) of the ATAD3B gene. This alteration results from a C to T substitution at nucleotide position 325, causing the arginine (R) at amino acid position 109 to be replaced by a tryptophan (W). 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

0.17

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Pathogenic

0.19

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.28

Eigen

Uncertain

0.42

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.84

LIST_S2

Pathogenic

0.99

M_CAP

Pathogenic

0.50

MetaRNN

Pathogenic

0.79

MetaSVM

Uncertain

0.64

MutationAssessor

Pathogenic

3.1

PrimateAI

Pathogenic

0.87

PROVEAN

Pathogenic

-6.3

REVEL

Pathogenic

0.69

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0010

Polyphen

1.0

Vest4

0.67

MutPred

0.23

Loss of MoRF binding (P = 0.0628);

MVP

0.90

MPC

2.0

ClinPred

0.95

GERP RS

2.7

Varity_R

0.62

gMVP

0.088

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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