Genetic Variant ATAD3B:p.Ala16Val (chr1-1471931-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_031921.6(ATAD3B):c.47C>T(p.Ala16Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000662 in 151,018 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 30)

Exomes 𝑓: 0.0 ( 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: 0.546

Publications

0 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.22216234).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATAD3B	NM_031921.6 link	c.47C>T	p.Ala16Val	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
ATAD3B	ENST00000673477.1 link	c.47C>T	p.Ala16Val	missense_variant	Exon 1 of 16		NM_031921.6	ENSP00000500094.1		Q5T9A4-1
ATAD3B	ENST00000308647.8 link	c.47C>T	p.Ala16Val	missense_variant	Exon 1 of 14	1		ENSP00000311766.8		A0A5K1VW56

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000659

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

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1092562

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

517342

African (AFR)

AF:

0.00

AC:

AN:

22636

American (AMR)

AF:

0.00

AC:

AN:

8538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14052

East Asian (EAS)

AF:

0.00

AC:

AN:

25868

South Asian (SAS)

AF:

0.00

AC:

AN:

20242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2888

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

921700

Other (OTH)

AF:

0.00

AC:

AN:

43396

GnomAD4 genome

AF:

0.00000662

AC:

AN:

151018

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73752

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41060

American (AMR)

AF:

0.0000659

AC:

AN:

15176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5096

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10470

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67668

Other (OTH)

AF:

0.00

AC:

AN:

2066

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 03, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.47C>T (p.A16V) alteration is located in exon 1 (coding exon 1) of the ATAD3B gene. This alteration results from a C to T substitution at nucleotide position 47, causing the alanine (A) at amino acid position 16 to be replaced by a valine (V). 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

0.093

BayesDel_addAF

Benign

-0.061

BayesDel_noAF

Benign

-0.33

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.57

M_CAP

Pathogenic

0.87

MetaRNN

Benign

0.22

MetaSVM

Benign

-0.66

MutationAssessor

Benign

1.1

PhyloP100

0.55

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.3

REVEL

Benign

0.20

Sift

Benign

0.23

Sift4G

Uncertain

0.024

Polyphen

0.52

Vest4

0.084

MutPred

0.16

Loss of glycosylation at P18 (P = 0.1241);

MVP

0.66

MPC

0.85

ClinPred

0.21

GERP RS

2.6

PromoterAI

0.033

Neutral

(source)

Varity_R

0.045

gMVP

0.060

Mutation Taster

=92/8

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over