17-30834178-A-G

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_024857.5(ATAD5):ā€‹c.97A>Gā€‹(p.Thr33Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000241 in 1,578,786 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: š‘“ 0.000026 ( 0 hom., cov: 32)
Exomes š‘“: 0.000024 ( 0 hom. )

Consequence

ATAD5
NM_024857.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.526
Variant links:
Genes affected
ATAD5 (HGNC:25752): (ATPase family AAA domain containing 5) Enables DNA clamp unloader activity. Involved in DNA clamp unloading; positive regulation of DNA replication; and positive regulation of cell cycle G2/M phase transition. Part of Elg1 RFC-like complex. Biomarker of neurilemmoma. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.008314699).
BS2
High AC in GnomAdExome4 at 34 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ATAD5NM_024857.5 linkuse as main transcriptc.97A>G p.Thr33Ala missense_variant 2/23 ENST00000321990.5 NP_079133.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ATAD5ENST00000321990.5 linkuse as main transcriptc.97A>G p.Thr33Ala missense_variant 2/231 NM_024857.5 ENSP00000313171 P1Q96QE3-1
ATAD5ENST00000578295.5 linkuse as main transcriptc.97A>G p.Thr33Ala missense_variant 2/151 ENSP00000463102

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152192
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000577
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000403
AC:
9
AN:
223232
Hom.:
0
AF XY:
0.0000329
AC XY:
4
AN XY:
121426
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000384
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000178
Gnomad SAS exome
AF:
0.0000406
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000377
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000238
AC:
34
AN:
1426476
Hom.:
0
Cov.:
29
AF XY:
0.0000297
AC XY:
21
AN XY:
707932
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000281
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000154
Gnomad4 SAS exome
AF:
0.0000381
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000200
Gnomad4 OTH exome
AF:
0.0000340
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152310
Hom.:
0
Cov.:
32
AF XY:
0.00
AC XY:
0
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000578
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.0000412
AC:
5
Asia WGS
AF:
0.000866
AC:
3
AN:
3478

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsMay 18, 2023The c.97A>G (p.T33A) alteration is located in exon 2 (coding exon 2) of the ATAD5 gene. This alteration results from a A to G substitution at nucleotide position 97, causing the threonine (T) at amino acid position 33 to be replaced by an alanine (A). 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
0.071
BayesDel_addAF
Benign
-0.51
T
BayesDel_noAF
Benign
-0.70
CADD
Benign
12
DANN
Benign
0.77
DEOGEN2
Benign
0.033
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-0.97
FATHMM_MKL
Benign
0.073
N
LIST_S2
Benign
0.49
T
M_CAP
Benign
0.0025
T
MetaRNN
Benign
0.0083
T
MetaSVM
Benign
-0.97
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.28
T
PROVEAN
Benign
-0.38
N
REVEL
Benign
0.069
Sift
Benign
0.65
T
Sift4G
Benign
0.78
T
Polyphen
0.0020
B
Vest4
0.13
MVP
0.12
MPC
0.070
ClinPred
0.014
T
GERP RS
0.50
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.041
gMVP
0.047

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: rs200684468; hg19: chr17-29161196; COSMIC: COSV58978189; COSMIC: COSV58978189; API