Genetic Variant NM_001170535.3:c.125C>T (chr1-1512393-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001170535.3(ATAD3A):c.125C>T(p.Ala42Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 29)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

ATAD3A
NM_001170535.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.171

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

Harel-Yoon syndrome
Inheritance: AR, AD, SD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae)
pontocerebellar hypoplasia, hypotonia, and respiratory insufficiency syndrome, neonatal lethal
Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ATAD3A links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.20860213).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170535.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATAD3A	NM_001170535.3	MANE Select	c.125C>T	p.Ala42Val	missense	Exon 1 of 16	NP_001164006.1	Q9NVI7-2
ATAD3A	NM_018188.5		c.125C>T	p.Ala42Val	missense	Exon 1 of 16	NP_060658.3
ATAD3A	NM_001170536.3		c.-330C>T		upstream_gene	N/A	NP_001164007.1	Q9NVI7-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
ATAD3A	ENST00000378756.8	TSL:1 MANE Select	c.125C>T	p.Ala42Val	missense	Exon 1 of 16	ENSP00000368031.3	Q9NVI7-2
ATAD3A	ENST00000378755.9	TSL:2	c.125C>T	p.Ala42Val	missense	Exon 1 of 16	ENSP00000368030.5	Q9NVI7-1
ATAD3A	ENST00000936382.1		c.125C>T	p.Ala42Val	missense	Exon 1 of 16	ENSP00000606441.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

9912

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

1086698

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

516122

African (AFR)

AF:

0.00

AC:

AN:

22196

American (AMR)

AF:

0.00

AC:

AN:

7866

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

13564

East Asian (EAS)

AF:

0.00

AC:

AN:

25050

South Asian (SAS)

AF:

0.00

AC:

AN:

19972

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34054

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2854

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

918430

Other (OTH)

AF:

0.00

AC:

AN:

42712

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.093

BayesDel_addAF

Benign

-0.12

BayesDel_noAF

Benign

-0.42

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0053

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.60

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.79

M_CAP

Pathogenic

0.84

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.4

PhyloP100

-0.17

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-0.85

REVEL

Benign

0.18

Sift

Benign

0.22

Sift4G

Benign

0.24

Polyphen

0.54

Vest4

0.13

MutPred

0.17

Gain of methylation at K44 (P = 0.0995)

MVP

0.82

MPC

0.55

ClinPred

0.21

GERP RS

0.60

PromoterAI

-0.036

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.058

gMVP

0.23

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over