Variant chr1-1512376-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001170535.3(ATAD3A):c.108G>C(p.Gly36=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.162 in 1,220,110 control chromosomes in the GnomAD database, including 33,465 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.34 ( 14097 hom., cov: 30)

Exomes 𝑓: 0.14 ( 19368 hom. )

Consequence

ATAD3A
NM_001170535.3 synonymous

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0330

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 Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 1-1512376-G-C is Benign according to our data. Variant chr1-1512376-G-C is described in ClinVar as [Benign]. Clinvar id is 2688185.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.033 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD3A	NM_001170535.3 linkuse as main transcript	c.108G>C	p.Gly36=	synonymous_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.108G>C	p.Gly36=	synonymous_variant	1/16	1	NM_001170535.3	ENSP00000368031	P1	Q9NVI7-2
ATAD3A	ENST00000378755.9 linkuse as main transcript	c.108G>C	p.Gly36=	synonymous_variant	1/16	2		ENSP00000368030		Q9NVI7-1
ATAD3A	ENST00000672388.1 linkuse as main transcript	n.212G>C		non_coding_transcript_exon_variant	1/14
ATAD3A	ENST00000339113.9 linkuse as main transcript			upstream_gene_variant		2		ENSP00000339421

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

50828

AN:

150364

Hom.:

14049

Cov.:

show subpopulations

Gnomad AFR

AF:

0.741

Gnomad AMI

AF:

0.121

Gnomad AMR

AF:

0.334

Gnomad ASJ

AF:

0.122

Gnomad EAS

AF:

0.514

Gnomad SAS

AF:

0.361

Gnomad FIN

AF:

0.209

Gnomad MID

AF:

0.169

Gnomad NFE

AF:

0.117

Gnomad OTH

AF:

0.295

GnomAD3 exomes

AF:

0.127

AC:

1237

AN:

9776

Hom.:

119

AF XY:

0.128

AC XY:

633

AN XY:

4948

show subpopulations

Gnomad AFR exome

AF:

0.706

Gnomad AMR exome

AF:

0.0536

Gnomad ASJ exome

AF:

0.0104

Gnomad EAS exome

AF:

0.0714

Gnomad SAS exome

AF:

0.136

Gnomad FIN exome

AF:

0.144

Gnomad NFE exome

AF:

0.0463

Gnomad OTH exome

AF:

0.115

GnomAD4 exome

AF:

0.138

AC:

147271

AN:

1069642

Hom.:

19368

Cov.:

AF XY:

0.137

AC XY:

69551

AN XY:

508642

show subpopulations

Gnomad4 AFR exome

AF:

0.782

Gnomad4 AMR exome

AF:

0.348

Gnomad4 ASJ exome

AF:

0.118

Gnomad4 EAS exome

AF:

0.481

Gnomad4 SAS exome

AF:

0.331

Gnomad4 FIN exome

AF:

0.201

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.198

GnomAD4 genome

AF:

0.339

AC:

50934

AN:

150468

Hom.:

14097

Cov.:

AF XY:

0.344

AC XY:

25301

AN XY:

73484

show subpopulations

Gnomad4 AFR

AF:

0.742

Gnomad4 AMR

AF:

0.334

Gnomad4 ASJ

AF:

0.122

Gnomad4 EAS

AF:

0.514

Gnomad4 SAS

AF:

0.360

Gnomad4 FIN

AF:

0.209

Gnomad4 NFE

AF:

0.117

Gnomad4 OTH

AF:

0.296

Alfa

AF:

0.0781

Hom.:

Bravo

AF:

0.367

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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 40% of patients studied by a panel of primary immunodeficiencies. Number of patients: 38. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.7

DANN

Benign

0.42

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.6

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