Variant 1-1478722-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_031921.6(ATAD3B):c.361G>A(p.Glu121Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000157 in 1,528,562 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000071 ( 0 hom., cov: 24)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ATAD3B
NM_031921.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.47

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD3B	NM_031921.6 linkuse as main transcript	c.361G>A	p.Glu121Lys	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.361G>A	p.Glu121Lys	missense_variant	3/16		NM_031921.6	ENSP00000500094.1	Q5T9A4-1
ATAD3B	ENST00000308647.8 linkuse as main transcript	c.282+1372G>A		intron_variant		1		ENSP00000311766.8	A0A5K1VW56
ATAD3B	ENST00000472194.6 linkuse as main transcript	n.697G>A		non_coding_transcript_exon_variant	1/14	1

Frequencies

GnomAD3 genomes

AF:

0.00000706

AC:

AN:

141728

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000153

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000134

AC:

AN:

149408

Hom.:

AF XY:

0.00

AC XY:

AN XY:

79400

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000410

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000179

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000166

AC:

AN:

1386834

Hom.:

Cov.:

AF XY:

0.00000879

AC XY:

AN XY:

682338

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000283

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000196

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000706

AC:

AN:

141728

Hom.:

Cov.:

AF XY:

0.0000146

AC XY:

AN XY:

68638

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000153

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000416

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

May 05, 2023

The c.361G>A (p.E121K) alteration is located in exon 3 (coding exon 3) of the ATAD3B gene. This alteration results from a G to A substitution at nucleotide position 361, causing the glutamic acid (E) at amino acid position 121 to be replaced by a lysine (K). 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

0.48

BayesDel_addAF

Uncertain

0.055

BayesDel_noAF

Uncertain

-0.040

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.085

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.073

MetaRNN

Uncertain

0.49

MetaSVM

Benign

-0.34

MutationAssessor

Uncertain

2.8

PrimateAI

Pathogenic

0.91

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.31

Sift

Benign

0.033

Sift4G

Benign

0.079

Polyphen

0.98

Vest4

0.54

MutPred

0.24

Gain of loop (P = 3e-04);

MVP

0.80

MPC

1.4

ClinPred

0.82

GERP RS

2.7

Varity_R

0.41

gMVP

0.070

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