Variant 17-30834499-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBP6BS2

The ENST00000321990.5(ATAD5):c.418G>A(p.Asp140Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,584,994 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 7 hom. )

Consequence

ATAD5
ENST00000321990.5 missense

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 3.08

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 -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.007975161).

BP6

Variant 17-30834499-G-A is Benign according to our data. Variant chr17-30834499-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3043100.Status of the report is no_assertion_criteria_provided, 0 stars.

BS2

High AC in GnomAd4 at 336 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD5	NM_024857.5 linkuse as main transcript	c.418G>A	p.Asp140Asn	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.418G>A	p.Asp140Asn	missense_variant	2/23	1	NM_024857.5	ENSP00000313171	P1	Q96QE3-1
ATAD5	ENST00000578295.5 linkuse as main transcript	c.418G>A	p.Asp140Asn	missense_variant	2/15	1		ENSP00000463102
	ENST00000580873.1 linkuse as main transcript	n.464C>T		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.00221

AC:

336

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00434

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00370

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00252

AC:

568

AN:

224986

Hom.:

AF XY:

0.00240

AC XY:

293

AN XY:

121992

show subpopulations

Gnomad AFR exome

AF:

0.000578

Gnomad AMR exome

AF:

0.000371

Gnomad ASJ exome

AF:

0.000118

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000319

Gnomad FIN exome

AF:

0.00410

Gnomad NFE exome

AF:

0.00422

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00344

AC:

4929

AN:

1432724

Hom.:

Cov.:

AF XY:

0.00332

AC XY:

2366

AN XY:

712346

show subpopulations

Gnomad4 AFR exome

AF:

0.000602

Gnomad4 AMR exome

AF:

0.000408

Gnomad4 ASJ exome

AF:

0.000121

Gnomad4 EAS exome

AF:

0.0000759

Gnomad4 SAS exome

AF:

0.000224

Gnomad4 FIN exome

AF:

0.00479

Gnomad4 NFE exome

AF:

0.00408

Gnomad4 OTH exome

AF:

0.00211

GnomAD4 genome

AF:

0.00221

AC:

336

AN:

152270

Hom.:

Cov.:

AF XY:

0.00189

AC XY:

141

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000602

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00434

Gnomad4 NFE

AF:

0.00371

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00337

Hom.:

Bravo

AF:

0.00192

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00441

AC:

ESP6500AA

AF:

0.00159

AC:

ESP6500EA

AF:

0.00419

AC:

ExAC

AF:

0.00277

AC:

336

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

ATAD5-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 02, 2020

This variant is classified as likely 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

0.086

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.26

Eigen

Uncertain

0.54

Eigen_PC

Uncertain

0.50

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

M_CAP

Benign

0.010

MetaRNN

Benign

0.0080

MetaSVM

Benign

-0.92

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.68

PrimateAI

Benign

0.34

PROVEAN

Benign

-2.2

REVEL

Benign

0.14

Sift

Uncertain

0.0010

Sift4G

Benign

0.36

Polyphen

1.0

Vest4

0.18

MVP

0.37

MPC

0.25

ClinPred

0.032

GERP RS

5.8

Varity_R

0.15

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