17-30834464-C-G

Variant names:

• chr17-30834464-C-G
• NM_024857.5:c.383C>G

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.144

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]

ENSG00000265334 (HGNC:):

ACMG classification

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
ATAD5	NM_024857.5	c.383C>G	p.Thr128Ser	missense_variant	Exon 2 of 23	ENST00000321990.5	NP_079133.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATAD5	ENST00000321990.5	c.383C>G	p.Thr128Ser	missense_variant	Exon 2 of 23	1	NM_024857.5	ENSP00000313171.4
ATAD5	ENST00000578295.5	n.383C>G		non_coding_transcript_exon_variant	Exon 2 of 15	1		ENSP00000463102.1
ENSG00000265334	ENST00000580873.1	n.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

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;