Variant chr1-1512399-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001170535.3(ATAD3A):c.131A>G(p.Lys44Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000154 in 1,235,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 29)

Exomes 𝑓: 0.000017 ( 0 hom. )

Consequence

ATAD3A
NM_001170535.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.20

Variant links:

Genes affected

ATAD3A (HGNC:25567): (ATPase family AAA domain containing 3A) This gene encodes a ubiquitously expressed mitochondrial membrane protein that contributes to mitochondrial dynamics, nucleoid organization, protein translation, cell growth, and cholesterol metabolism. This gene is a member of the ATPase family AAA-domain containing 3 gene family which, in humans, includes two other paralogs. Naturally occurring mutations in this gene are associated with distinct neurological syndromes including Harel-Yoon syndrome. High-level expression of this gene is associated with poor survival in breast cancer patients. A homozygous knockout of the orthologous gene in mice results in embryonic lethality at day 7.5 due to growth retardation and defective development of the trophoblast lineage. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2017]

ATAD3A links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26248944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD3A	NM_001170535.3 linkuse as main transcript	c.131A>G	p.Lys44Arg	missense_variant	1/16	ENST00000378756.8	NP_001164006.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATAD3A	ENST00000378756.8 linkuse as main transcript	c.131A>G	p.Lys44Arg	missense_variant	1/16	1	NM_001170535.3	ENSP00000368031	P1	Q9NVI7-2
ATAD3A	ENST00000378755.9 linkuse as main transcript	c.131A>G	p.Lys44Arg	missense_variant	1/16	2		ENSP00000368030		Q9NVI7-1
ATAD3A	ENST00000672388.1 linkuse as main transcript	n.235A>G		non_coding_transcript_exon_variant	1/14
ATAD3A	ENST00000339113.9 linkuse as main transcript	c.17A>G	p.Lys6Arg	missense_variant, NMD_transcript_variant	1/17	2		ENSP00000339421

Frequencies

GnomAD3 genomes

AF:

0.00000665

AC:

AN:

150454

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:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000166

AC:

AN:

1085286

Hom.:

Cov.:

AF XY:

0.0000155

AC XY:

AN XY:

515380

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00

Gnomad4 NFE exome

AF:

0.0000196

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000665

AC:

AN:

150454

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

73422

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:

0.0000148

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Harel-Yoon syndrome

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Baylor Genetics

Oct 19, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.079

BayesDel_addAF

Benign

0.00029

BayesDel_noAF

Benign

-0.24

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0029

.;T

Eigen

Benign

0.045

Eigen_PC

Benign

0.13

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;D

M_CAP

Pathogenic

0.71

MetaRNN

Benign

0.26

T;T

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

0.95

L;L

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.56

N;N

REVEL

Benign

0.16

Sift

Benign

0.28

T;T

Sift4G

Benign

0.63

T;T

Polyphen

0.98

.;D

Vest4

0.20

MutPred

0.13

Loss of ubiquitination at K44 (P = 0.0043);Loss of ubiquitination at K44 (P = 0.0043);

MVP

0.89

MPC

0.95

ClinPred

0.90

GERP RS

3.9

Varity_R

0.32

gMVP

0.37

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