17-30834340-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_024857.5(ATAD5):c.259C>T(p.Pro87Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,609,988 control chromosomes in the GnomAD database, including 13,291 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.13 (1452 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11839 hom.)
• Consequence: ATAD5 NM_024857.5 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.100

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027531087).
• BP6: Variant 17-30834340-C-T is Benign according to our data. Variant chr17-30834340-C-T is described in ClinVar as [Benign]. Clinvar id is 3059655.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATAD5	NM_024857.5	c.259C>T	p.Pro87Ser	missense_variant	2/23	ENST00000321990.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATAD5	ENST00000321990.5	c.259C>T	p.Pro87Ser	missense_variant	2/23	1	NM_024857.5	P1
ATAD5	ENST00000578295.5	c.259C>T	p.Pro87Ser	missense_variant	2/15	1
	ENST00000580873.1	n.623G>A		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 19959 AN: 150250 Hom.: 1442 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0875

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.0980

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.124

GnomAD3 exomes AF: 0.137 AC: 34064 AN: 249084 Hom.: 2695 AF XY: 0.138 AC XY: 18574 AN XY: 134650

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.0871

Gnomad EAS exome AF: 0.123

Gnomad SAS exome AF: 0.247

Gnomad FIN exome AF: 0.0856

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.119 AC: 174395 AN: 1459614 Hom.: 11839 Cov.: 32 AF XY: 0.122 AC XY: 88744 AN XY: 726012

Gnomad4 AFR exome AF: 0.165

Gnomad4 AMR exome AF: 0.173

Gnomad4 ASJ exome AF: 0.0890

Gnomad4 EAS exome AF: 0.161

Gnomad4 SAS exome AF: 0.243

Gnomad4 FIN exome AF: 0.0879

Gnomad4 NFE exome AF: 0.107

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.133 AC: 20011 AN: 150374 Hom.: 1452 Cov.: 32 AF XY: 0.134 AC XY: 9875 AN XY: 73484

Gnomad4 AFR AF: 0.167

Gnomad4 AMR AF: 0.164

Gnomad4 ASJ AF: 0.0875

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.246

Gnomad4 FIN AF: 0.0884

Gnomad4 NFE AF: 0.107

Gnomad4 OTH AF: 0.126

Alfa AF: 0.111 Hom.: 2585

Bravo AF: 0.136

TwinsUK AF: 0.108 AC: 402

ALSPAC AF: 0.105 AC: 403

ESP6500AA AF: 0.166 AC: 730

ESP6500EA AF: 0.105 AC: 902

ExAC AF: 0.140 AC: 16974

Asia WGS AF: 0.195 AC: 678 AN: 3478

EpiCase AF: 0.103

EpiControl AF: 0.103

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

ATAD5-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 18, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
Cadd	Benign	0.73
Dann	Benign	0.61
DEOGEN2	Benign	0.028	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.3	N
MutationTaster	Benign	1.0	P
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.043
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.036
MPC		0.070
ClinPred		0.0030	T
GERP RS		1.4
Varity_R		0.025
gMVP		0.043

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: rs3816780; hg19: chr17-29161358; COSMIC: COSV58972907; COSMIC: COSV58972907;