Variant 17-30834184-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_024857.5(ATAD5):c.103A>T(p.Thr35Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 1,583,100 control chromosomes in the GnomAD database, including 23,021 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 0.23 ( 6128 hom., cov: 32)

Exomes 𝑓: 0.13 ( 16893 hom. )

Consequence

ATAD5
NM_024857.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.862

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013140142).

BP6

Variant 17-30834184-A-T is Benign according to our data. Variant chr17-30834184-A-T is described in ClinVar as [Benign]. Clinvar id is 3060175.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATAD5	NM_024857.5 linkuse as main transcript	c.103A>T	p.Thr35Ser	missense_variant	2/23	ENST00000321990.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATAD5	ENST00000321990.5 linkuse as main transcript	c.103A>T	p.Thr35Ser	missense_variant	2/23	1	NM_024857.5	P1	Q96QE3-1
ATAD5	ENST00000578295.5 linkuse as main transcript	c.103A>T	p.Thr35Ser	missense_variant	2/15	1

Frequencies

GnomAD3 genomes

AF:

0.231

AC:

35046

AN:

152008

Hom.:

6092

Cov.:

show subpopulations

Gnomad AFR

AF:

0.487

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.209

Gnomad ASJ

AF:

0.0950

Gnomad EAS

AF:

0.131

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.0945

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.115

Gnomad OTH

AF:

0.201

GnomAD3 exomes

AF:

0.166

AC:

37685

AN:

226368

Hom.:

4490

AF XY:

0.162

AC XY:

19884

AN XY:

122976

show subpopulations

Gnomad AFR exome

AF:

0.503

Gnomad AMR exome

AF:

0.195

Gnomad ASJ exome

AF:

0.0910

Gnomad EAS exome

AF:

0.123

Gnomad SAS exome

AF:

0.276

Gnomad FIN exome

AF:

0.0925

Gnomad NFE exome

AF:

0.115

Gnomad OTH exome

AF:

0.142

GnomAD4 exome

AF:

0.134

AC:

192342

AN:

1430974

Hom.:

16893

Cov.:

AF XY:

0.137

AC XY:

97023

AN XY:

710470

show subpopulations

Gnomad4 AFR exome

AF:

0.502

Gnomad4 AMR exome

AF:

0.195

Gnomad4 ASJ exome

AF:

0.0953

Gnomad4 EAS exome

AF:

0.161

Gnomad4 SAS exome

AF:

0.272

Gnomad4 FIN exome

AF:

0.0938

Gnomad4 NFE exome

AF:

0.113

Gnomad4 OTH exome

AF:

0.153

GnomAD4 genome

AF:

0.231

AC:

35146

AN:

152126

Hom.:

6128

Cov.:

AF XY:

0.229

AC XY:

17035

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.488

Gnomad4 AMR

AF:

0.209

Gnomad4 ASJ

AF:

0.0950

Gnomad4 EAS

AF:

0.132

Gnomad4 SAS

AF:

0.270

Gnomad4 FIN

AF:

0.0945

Gnomad4 NFE

AF:

0.115

Gnomad4 OTH

AF:

0.203

Alfa

AF:

0.133

Hom.:

1346

Bravo

AF:

0.248

TwinsUK

AF:

0.113

AC:

418

ALSPAC

AF:

0.111

AC:

428

ESP6500AA

AF:

0.477

AC:

2097

ESP6500EA

AF:

0.112

AC:

960

ExAC

AF:

0.178

AC:

21653

Asia WGS

AF:

0.236

AC:

820

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

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

0.062

BayesDel_addAF

Benign

-0.74

BayesDel_noAF

Benign

-0.69

CADD

Benign

DANN

Benign

0.86

DEOGEN2

Benign

0.044

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.15

MetaRNN

Benign

0.0013

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-2.3

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Benign

0.81

REVEL

Benign

0.15

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.032

MutPred

0.035

Gain of phosphorylation at T35 (P = 0.0502);

MPC

0.064

ClinPred

0.0013

GERP RS

5.5

Varity_R

0.030

gMVP

0.092

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