1-1454423-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001039211.3(ATAD3C):​c.301G>A​(p.Ala101Thr) variant causes a missense change. The variant allele was found at a frequency of 0.0000143 in 1,609,282 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

ATAD3C
NM_001039211.3 missense

Scores

9
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.84
Variant links:
Genes affected
ATAD3C (HGNC:32151): (ATPase family AAA domain containing 3C) Predicted to enable zinc ion binding activity. Predicted to be involved in mitochondrion organization. Located in mitochondrion. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATAD3CNM_001039211.3 linkc.301G>A p.Ala101Thr missense_variant Exon 4 of 12 ENST00000378785.7 NP_001034300.2 Q5T2N8

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATAD3CENST00000378785.7 linkc.301G>A p.Ala101Thr missense_variant Exon 4 of 12 2 NM_001039211.3 ENSP00000368062.2 Q5T2N8
ATAD3CENST00000475091.2 linkc.223-1037G>A intron_variant Intron 4 of 5 5 ENSP00000464661.1 J3QSF3

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
151956
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000657
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
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
GnomAD3 exomes
AF:
0.0000165
AC:
4
AN:
242480
Hom.:
0
AF XY:
0.0000304
AC XY:
4
AN XY:
131756
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000111
Gnomad SAS exome
AF:
0.0000672
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000130
AC:
19
AN:
1457210
Hom.:
0
Cov.:
33
AF XY:
0.0000152
AC XY:
11
AN XY:
724726
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000152
Gnomad4 SAS exome
AF:
0.0000350
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000166
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152072
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74346
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.000476
Bravo
AF:
0.00000756
ExAC
AF:
0.0000248
AC:
3

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 07, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.301G>A (p.A101T) alteration is located in exon 4 (coding exon 4) of the ATAD3C gene. This alteration results from a G to A substitution at nucleotide position 301, causing the alanine (A) at amino acid position 101 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.092
BayesDel_addAF
Benign
-0.073
T
BayesDel_noAF
Uncertain
-0.070
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.030
T
Eigen
Benign
0.099
Eigen_PC
Benign
-0.045
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Uncertain
0.91
D
M_CAP
Benign
0.040
D
MetaRNN
Uncertain
0.54
D
MetaSVM
Uncertain
0.59
D
MutationAssessor
Benign
1.1
L
PrimateAI
Uncertain
0.59
T
PROVEAN
Uncertain
-2.8
D
REVEL
Uncertain
0.60
Sift
Benign
0.093
T
Sift4G
Benign
0.16
T
Polyphen
0.94
P
Vest4
0.62
MutPred
0.30
Loss of helix (P = 0.079);
MVP
0.91
MPC
0.28
ClinPred
0.52
D
GERP RS
2.5
Varity_R
0.21
gMVP
0.079

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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: rs781740791; hg19: chr1-1389803; API