17-30834464-C-G

Variant summary

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

The NM_024857.5(ATAD5):​c.383C>G​(p.Thr128Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

ATAD5
NM_024857.5 missense

Scores

19

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.144
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]

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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=0.022487253).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ATAD5NM_024857.5 linkc.383C>G p.Thr128Ser missense_variant Exon 2 of 23 ENST00000321990.5 NP_079133.3 Q96QE3-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ATAD5ENST00000321990.5 linkc.383C>G p.Thr128Ser missense_variant Exon 2 of 23 1 NM_024857.5 ENSP00000313171.4 Q96QE3-1
ATAD5ENST00000578295.5 linkn.383C>G non_coding_transcript_exon_variant Exon 2 of 15 1 ENSP00000463102.1 A0A075B754
ENSG00000265334ENST00000580873.1 linkn.499G>C non_coding_transcript_exon_variant Exon 2 of 2 2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 07, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.383C>G (p.T128S) alteration is located in exon 2 (coding exon 2) of the ATAD5 gene. This alteration results from a C to G substitution at nucleotide position 383, causing the threonine (T) at amino acid position 128 to be replaced by a serine (S). 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
0.12
BayesDel_addAF
Benign
-0.35
T
BayesDel_noAF
Benign
-0.73
CADD
Benign
8.0
DANN
Benign
0.72
DEOGEN2
Benign
0.055
T
Eigen
Benign
-0.86
Eigen_PC
Benign
-0.84
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.56
T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.022
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
1.8
L
PrimateAI
Benign
0.26
T
PROVEAN
Benign
-0.56
N
REVEL
Benign
0.10
Sift
Benign
0.49
T
Sift4G
Benign
0.73
T
Polyphen
0.013
B
Vest4
0.051
MutPred
0.078
Gain of relative solvent accessibility (P = 0.0479);
MVP
0.29
MPC
0.078
ClinPred
0.060
T
GERP RS
0.066
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.038
gMVP
0.062

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-29161482; API