17-30834287-C-G

Variant names:

• chr17-30834287-C-G
• rs1431268072
• NM_024857.5:c.206C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_024857.5(ATAD5):​c.206C>G​(p.Thr69Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000131 in 152,122 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: 𝑓 0.000013 (0 hom., cov: 32)
• Consequence: ATAD5 NM_024857.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.82

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24234596).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATAD5	NM_024857.5	c.206C>G	p.Thr69Ser	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.206C>G	p.Thr69Ser	missense_variant	Exon 2 of 23	1	NM_024857.5	ENSP00000313171.4
ATAD5	ENST00000578295.5	n.206C>G		non_coding_transcript_exon_variant	Exon 2 of 15	1		ENSP00000463102.1
ENSG00000265334	ENST00000580873.1	n.*38G>C		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152122 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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

GnomAD4 exome Cov.: 32

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152122 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74304

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000385

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 01, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.206C>G (p.T69S) 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 206, causing the threonine (T) at amino acid position 69 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	0.20
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Uncertain	24
DANN	Benign	0.75
DEOGEN2	Benign	0.22	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0093	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.16	T
Polyphen		1.0	D
Vest4		0.30
MutPred		0.080		Loss of methylation at K68 (P = 0.1221);
MVP		0.31
MPC		0.27
ClinPred		0.90	D
GERP RS		4.9
Varity_R		0.35
gMVP		0.091

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

Other links and lift over

dbSNP: rs1431268072; hg19: chr17-29161305;