Variant chr1-1512459-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001170535.3(ATAD3A):c.191A>C(p.Glu64Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000384 in 1,042,564 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: not found (cov: 29)

Exomes 𝑓: 0.0000038 ( 0 hom. )

Consequence

ATAD3A
NM_001170535.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.11

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.42349762).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD3A	NM_001170535.3 linkuse as main transcript	c.191A>C	p.Glu64Ala	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.191A>C	p.Glu64Ala	missense_variant	1/16	1	NM_001170535.3	ENSP00000368031	P1	Q9NVI7-2
ATAD3A	ENST00000378755.9 linkuse as main transcript	c.191A>C	p.Glu64Ala	missense_variant	1/16	2		ENSP00000368030		Q9NVI7-1
ATAD3A	ENST00000672388.1 linkuse as main transcript	n.295A>C		non_coding_transcript_exon_variant	1/14
ATAD3A	ENST00000339113.9 linkuse as main transcript	c.77A>C	p.Glu26Ala	missense_variant, NMD_transcript_variant	1/17	2		ENSP00000339421

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000384

AC:

AN:

1042564

Hom.:

Cov.:

AF XY:

0.00000406

AC XY:

AN XY:

493076

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:

0.00000448

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 17, 2021

The c.191A>C (p.E64A) alteration is located in exon 1 (coding exon 1) of the ATAD3A gene. This alteration results from a A to C substitution at nucleotide position 191, causing the glutamic acid (E) at amino acid position 64 to be replaced by an alanine (A). 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

0.059

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.46

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.95

D;D

M_CAP

Pathogenic

0.72

MetaRNN

Benign

0.42

T;T

MetaSVM

Uncertain

0.56

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-4.4

D;D

REVEL

Uncertain

0.34

Sift

Benign

0.13

T;T

Sift4G

Benign

0.084

T;T

Polyphen

0.99

.;D

Vest4

0.30

MutPred

0.18

Gain of MoRF binding (P = 0.0214);Gain of MoRF binding (P = 0.0214);

MVP

0.95

MPC

0.95

ClinPred

0.99

GERP RS

3.9

Varity_R

0.69

gMVP

0.66

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