Variant 17-30834827-G-A 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.746G>A(p.Arg249Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,402 control chromosomes in the GnomAD database, including 12,300 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 (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.11 ( 955 hom., cov: 32)

Exomes 𝑓: 0.12 ( 11345 hom. )

Consequence

ATAD5
NM_024857.5 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 2.47

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=0.0044242144).

BP6

Variant 17-30834827-G-A is Benign according to our data. Variant chr17-30834827-G-A is described in ClinVar as [Benign]. Clinvar id is 3059306.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.231 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.746G>A	p.Arg249Lys	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.746G>A	p.Arg249Lys	missense_variant	2/23	1	NM_024857.5	ENSP00000313171	P1	Q96QE3-1
ATAD5	ENST00000578295.5 linkuse as main transcript	c.746G>A	p.Arg249Lys	missense_variant	2/15	1		ENSP00000463102
	ENST00000580873.1 linkuse as main transcript	n.334-198C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.105

AC:

15959

AN:

152106

Hom.:

950

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0719

Gnomad AMI

AF:

0.163

Gnomad AMR

AF:

0.153

Gnomad ASJ

AF:

0.0864

Gnomad EAS

AF:

0.132

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.0872

Gnomad MID

AF:

0.0854

Gnomad NFE

AF:

0.106

Gnomad OTH

AF:

0.104

GnomAD3 exomes

AF:

0.130

AC:

32406

AN:

250168

Hom.:

2480

AF XY:

0.133

AC XY:

17984

AN XY:

135438

show subpopulations

Gnomad AFR exome

AF:

0.0699

Gnomad AMR exome

AF:

0.171

Gnomad ASJ exome

AF:

0.0866

Gnomad EAS exome

AF:

0.123

Gnomad SAS exome

AF:

0.245

Gnomad FIN exome

AF:

0.0856

Gnomad NFE exome

AF:

0.108

Gnomad OTH exome

AF:

0.118

GnomAD4 exome

AF:

0.117

AC:

170634

AN:

1461178

Hom.:

11345

Cov.:

AF XY:

0.120

AC XY:

87216

AN XY:

726862

show subpopulations

Gnomad4 AFR exome

AF:

0.0707

Gnomad4 AMR exome

AF:

0.168

Gnomad4 ASJ exome

AF:

0.0888

Gnomad4 EAS exome

AF:

0.161

Gnomad4 SAS exome

AF:

0.242

Gnomad4 FIN exome

AF:

0.0879

Gnomad4 NFE exome

AF:

0.107

Gnomad4 OTH exome

AF:

0.117

GnomAD4 genome

AF:

0.105

AC:

15993

AN:

152224

Hom.:

955

Cov.:

AF XY:

0.107

AC XY:

7976

AN XY:

74422

show subpopulations

Gnomad4 AFR

AF:

0.0720

Gnomad4 AMR

AF:

0.153

Gnomad4 ASJ

AF:

0.0864

Gnomad4 EAS

AF:

0.132

Gnomad4 SAS

AF:

0.242

Gnomad4 FIN

AF:

0.0872

Gnomad4 NFE

AF:

0.106

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.108

Hom.:

1635

Bravo

AF:

0.106

TwinsUK

AF:

0.108

AC:

401

ALSPAC

AF:

0.104

AC:

401

ESP6500AA

AF:

0.0736

AC:

324

ESP6500EA

AF:

0.104

AC:

895

ExAC

AF:

0.131

AC:

15919

Asia WGS

AF:

0.190

AC:

660

AN:

3478

EpiCase

AF:

0.102

EpiControl

AF:

0.102

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 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

0.079

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.65

CADD

Benign

6.1

DANN

Benign

0.58

DEOGEN2

Benign

0.075

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.58

FATHMM_MKL

Benign

0.22

LIST_S2

Benign

0.29

MetaRNN

Benign

0.0044

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.83

REVEL

Benign

0.044

Sift

Benign

0.17

Sift4G

Benign

0.84

Polyphen

0.16

Vest4

0.0070

MPC

0.071

ClinPred

0.0082

GERP RS

3.3

Varity_R

0.065

gMVP

0.093

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