Variant chr1-1516000-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001170535.3(ATAD3A):c.206-12T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,613,412 control chromosomes in the GnomAD database, including 52,037 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.35 ( 14797 hom., cov: 32)

Exomes 𝑓: 0.18 ( 37240 hom. )

Consequence

ATAD3A
NM_001170535.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00006045

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -4.17

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.93).

BP6

Variant 1-1516000-T-C is Benign according to our data. Variant chr1-1516000-T-C is described in ClinVar as [Benign]. Clinvar id is 1185402.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATAD3A	NM_001170535.3 linkuse as main transcript	c.206-12T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000378756.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATAD3A	ENST00000378756.8 linkuse as main transcript	c.206-12T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001170535.3	P1	Q9NVI7-2

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53633

AN:

152042

Hom.:

14744

Cov.:

show subpopulations

Gnomad AFR

AF:

0.745

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.352

Gnomad ASJ

AF:

0.141

Gnomad EAS

AF:

0.507

Gnomad SAS

AF:

0.365

Gnomad FIN

AF:

0.225

Gnomad MID

AF:

0.178

Gnomad NFE

AF:

0.137

Gnomad OTH

AF:

0.311

GnomAD3 exomes

AF:

0.276

AC:

69034

AN:

250102

Hom.:

13771

AF XY:

0.261

AC XY:

35299

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.762

Gnomad AMR exome

AF:

0.412

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.510

Gnomad SAS exome

AF:

0.340

Gnomad FIN exome

AF:

0.230

Gnomad NFE exome

AF:

0.134

Gnomad OTH exome

AF:

0.231

GnomAD4 exome

AF:

0.185

AC:

270122

AN:

1461252

Hom.:

37240

Cov.:

AF XY:

0.187

AC XY:

136263

AN XY:

726938

show subpopulations

Gnomad4 AFR exome

AF:

0.768

Gnomad4 AMR exome

AF:

0.404

Gnomad4 ASJ exome

AF:

0.137

Gnomad4 EAS exome

AF:

0.490

Gnomad4 SAS exome

AF:

0.341

Gnomad4 FIN exome

AF:

0.223

Gnomad4 NFE exome

AF:

0.133

Gnomad4 OTH exome

AF:

0.224

GnomAD4 genome

AF:

0.353

AC:

53748

AN:

152160

Hom.:

14797

Cov.:

AF XY:

0.359

AC XY:

26693

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.746

Gnomad4 AMR

AF:

0.352

Gnomad4 ASJ

AF:

0.141

Gnomad4 EAS

AF:

0.506

Gnomad4 SAS

AF:

0.364

Gnomad4 FIN

AF:

0.225

Gnomad4 NFE

AF:

0.137

Gnomad4 OTH

AF:

0.312

Alfa

AF:

0.181

Hom.:

1600

Bravo

AF:

0.380

Asia WGS

AF:

0.419

AC:

1457

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Jan 24, 2024

This variant is classified as Benign based on local population frequency. This variant was detected in 51% of patients studied by a panel of primary immunodeficiencies. Number of patients: 48. Only high quality variants are reported. -

Pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Harel-Yoon syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.93

CADD

Benign

0.93

DANN

Benign

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000060

dbscSNV1_RF

Benign

0.0040

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