Variant 17-30834485-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_024857.5(ATAD5):c.404A>G(p.Glu135Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 1,584,380 control chromosomes in the GnomAD database, including 86,655 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.25 ( 5751 hom., cov: 32)

Exomes 𝑓: 0.33 ( 80904 hom. )

Consequence

ATAD5
NM_024857.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 1.89

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]

ATAD5 links:

(HGNC:):

links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0022529364).

BP6

Variant 17-30834485-A-G is Benign according to our data. Variant chr17-30834485-A-G is described in ClinVar as [Benign]. Clinvar id is 3060074.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.343 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD5	NM_024857.5 linkuse as main transcript	c.404A>G	p.Glu135Gly	missense_variant	2/23	ENST00000321990.5	NP_079133.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ATAD5	ENST00000321990.5 linkuse as main transcript	c.404A>G	p.Glu135Gly	missense_variant	2/23	1	NM_024857.5	ENSP00000313171	P1	Q96QE3-1
ATAD5	ENST00000578295.5 linkuse as main transcript	c.404A>G	p.Glu135Gly	missense_variant	2/15	1		ENSP00000463102
	ENST00000580873.1 linkuse as main transcript	n.478T>C		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.249

AC:

37815

AN:

152032

Hom.:

5745

Cov.:

show subpopulations

Gnomad AFR

AF:

0.102

Gnomad AMI

AF:

0.289

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.362

Gnomad EAS

AF:

0.00173

Gnomad SAS

AF:

0.167

Gnomad FIN

AF:

0.311

Gnomad MID

AF:

0.275

Gnomad NFE

AF:

0.347

Gnomad OTH

AF:

0.269

GnomAD3 exomes

AF:

0.266

AC:

60300

AN:

226424

Hom.:

9444

AF XY:

0.271

AC XY:

33245

AN XY:

122794

show subpopulations

Gnomad AFR exome

AF:

0.0944

Gnomad AMR exome

AF:

0.229

Gnomad ASJ exome

AF:

0.348

Gnomad EAS exome

AF:

0.00143

Gnomad SAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.318

Gnomad NFE exome

AF:

0.345

Gnomad OTH exome

AF:

0.303

GnomAD4 exome

AF:

0.325

AC:

465840

AN:

1432230

Hom.:

80904

Cov.:

AF XY:

0.321

AC XY:

228914

AN XY:

712128

show subpopulations

Gnomad4 AFR exome

AF:

0.0937

Gnomad4 AMR exome

AF:

0.232

Gnomad4 ASJ exome

AF:

0.344

Gnomad4 EAS exome

AF:

0.00106

Gnomad4 SAS exome

AF:

0.175

Gnomad4 FIN exome

AF:

0.318

Gnomad4 NFE exome

AF:

0.359

Gnomad4 OTH exome

AF:

0.299

GnomAD4 genome

AF:

0.249

AC:

37827

AN:

152150

Hom.:

5751

Cov.:

AF XY:

0.244

AC XY:

18174

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.102

Gnomad4 AMR

AF:

0.246

Gnomad4 ASJ

AF:

0.362

Gnomad4 EAS

AF:

0.00173

Gnomad4 SAS

AF:

0.168

Gnomad4 FIN

AF:

0.311

Gnomad4 NFE

AF:

0.347

Gnomad4 OTH

AF:

0.265

Alfa

AF:

0.324

Hom.:

20781

Bravo

AF:

0.241

TwinsUK

AF:

0.371

AC:

1377

ALSPAC

AF:

0.360

AC:

1386

ESP6500AA

AF:

0.109

AC:

482

ESP6500EA

AF:

0.341

AC:

2931

ExAC

AF:

0.259

AC:

31426

Asia WGS

AF:

0.0830

AC:

292

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATAD5-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 21, 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

0.13

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.23

Eigen

Benign

0.18

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.56

MetaRNN

Benign

0.0023

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

MutationTaster

Benign

0.20

PrimateAI

Benign

0.26

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.079

Sift

Benign

0.038

Sift4G

Uncertain

0.036

Polyphen

0.96

Vest4

0.026

MPC

0.088

ClinPred

0.045

GERP RS

4.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.12

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over