Variant chr1-1512307-T-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 2P and 11B. PM2BP4_StrongBP6_ModerateBP7BS1

The NM_001170535.3(ATAD3A):c.39T>A(p.Gly13=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000189 in 1,255,354 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00097 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

ATAD3A
NM_001170535.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.675

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 -9 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 1-1512307-T-A is Benign according to our data. Variant chr1-1512307-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 2638020.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.675 with no splicing effect.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000972 (146/150244) while in subpopulation AFR AF= 0.00334 (137/40958). AF 95% confidence interval is 0.00289. There are 1 homozygotes in gnomad4. There are 64 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD3A	NM_001170535.3 linkuse as main transcript	c.39T>A	p.Gly13=	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.39T>A	p.Gly13=	synonymous_variant	1/16	1	NM_001170535.3	ENSP00000368031	P1	Q9NVI7-2
ATAD3A	ENST00000378755.9 linkuse as main transcript	c.39T>A	p.Gly13=	synonymous_variant	1/16	2		ENSP00000368030		Q9NVI7-1
ATAD3A	ENST00000672388.1 linkuse as main transcript	n.143T>A		non_coding_transcript_exon_variant	1/14

Frequencies

GnomAD3 genomes

AF:

0.000966

AC:

145

AN:

150146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00333

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000462

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:

0.00

Gnomad OTH

AF:

0.000966

GnomAD3 exomes

AF:

0.000406

AC:

AN:

29530

Hom.:

AF XY:

0.000299

AC XY:

AN XY:

16726

show subpopulations

Gnomad AFR exome

AF:

0.00789

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00259

GnomAD4 exome

AF:

0.0000823

AC:

AN:

1105110

Hom.:

Cov.:

AF XY:

0.0000876

AC XY:

AN XY:

525352

show subpopulations

Gnomad4 AFR exome

AF:

0.00306

Gnomad4 AMR exome

AF:

0.000390

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:

0.00

Gnomad4 OTH exome

AF:

0.000343

GnomAD4 genome

AF:

0.000972

AC:

146

AN:

150244

Hom.:

Cov.:

AF XY:

0.000872

AC XY:

AN XY:

73382

show subpopulations

Gnomad4 AFR

AF:

0.00334

Gnomad4 AMR

AF:

0.000461

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000956

Alfa

AF:

0.000971

Hom.:

Bravo

AF:

0.00115

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Apr 01, 2023

ATAD3A: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.4

DANN

Benign

0.68

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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