chr1-1512287-A-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001170535.3(ATAD3A):ā€‹c.19A>Cā€‹(p.Ile7Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000659 in 151,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 32)

Consequence

ATAD3A
NM_001170535.3 missense

Scores

1
2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.859
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]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.065599024).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATAD3ANM_001170535.3 linkuse as main transcriptc.19A>C p.Ile7Leu missense_variant 1/16 ENST00000378756.8 NP_001164006.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATAD3AENST00000378756.8 linkuse as main transcriptc.19A>C p.Ile7Leu missense_variant 1/161 NM_001170535.3 ENSP00000368031 P1Q9NVI7-2
ATAD3AENST00000378755.9 linkuse as main transcriptc.19A>C p.Ile7Leu missense_variant 1/162 ENSP00000368030 Q9NVI7-1
ATAD3AENST00000672388.1 linkuse as main transcriptn.123A>C non_coding_transcript_exon_variant 1/14

Frequencies

GnomAD3 genomes
AF:
0.00000659
AC:
1
AN:
151652
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.00
GnomAD4 exome
Cov.:
30
GnomAD4 genome
AF:
0.00000659
AC:
1
AN:
151652
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74064
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.00
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:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingGeneDxMar 31, 2022Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.084
BayesDel_addAF
Benign
-0.085
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
14
DANN
Benign
0.69
DEOGEN2
Benign
0.0027
.;T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.98
FATHMM_MKL
Benign
0.31
N
LIST_S2
Benign
0.73
T;T
M_CAP
Uncertain
0.20
D
MetaRNN
Benign
0.066
T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
0.79
N;N
MutationTaster
Benign
0.54
N;N
PrimateAI
Pathogenic
0.85
D
PROVEAN
Benign
-0.16
N;N
REVEL
Uncertain
0.29
Sift
Benign
0.64
T;T
Sift4G
Benign
0.65
T;T
Polyphen
0.0
.;B
Vest4
0.17
MutPred
0.15
Loss of sheet (P = 0.0817);Loss of sheet (P = 0.0817);
MVP
0.51
MPC
0.33
ClinPred
0.047
T
GERP RS
-2.2
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.090
gMVP
0.17

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.

Other links and lift over

dbSNP: rs201314162; hg19: chr1-1447667; API