1-1512376-G-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0330

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]

ACMG classification

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	UniProt
ATAD3A	NM_001170535.3	c.108G>C	p.Gly36=	synonymous_variant	1/16	ENST00000378756.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATAD3A	ENST00000378756.8	c.108G>C	p.Gly36=	synonymous_variant	1/16	1	NM_001170535.3	P1
ATAD3A	ENST00000378755.9	c.108G>C	p.Gly36=	synonymous_variant	1/16	2
ATAD3A	ENST00000672388.1	n.212G>C		non_coding_transcript_exon_variant	1/14
ATAD3A	ENST00000339113.9			upstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.338 AC: 50828 AN: 150364 Hom.: 14049 Cov.: 30

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

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.: 31 AF XY: 0.137 AC XY: 69551 AN XY: 508642

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.: 30 AF XY: 0.344 AC XY: 25301 AN XY: 73484

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.: 91

Bravo AF: 0.367

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

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

Other links and lift over

dbSNP: rs1240736; hg19: chr1-1447756; COSMIC: COSV100186080; COSMIC: COSV100186080;