Variant 17-30835058-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_024857.5(ATAD5):c.977C>T(p.Ala326Val) variant causes a missense change. The variant allele was found at a frequency of 0.00041 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00042 ( 0 hom. )

Consequence

ATAD5
NM_024857.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.64

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 41 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ATAD5	NM_024857.5 linkuse as main transcript	c.977C>T	p.Ala326Val	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.977C>T	p.Ala326Val	missense_variant	2/23	1	NM_024857.5	ENSP00000313171	P1	Q96QE3-1
ATAD5	ENST00000578295.5 linkuse as main transcript	c.977C>T	p.Ala326Val	missense_variant	2/15	1		ENSP00000463102
	ENST00000580873.1 linkuse as main transcript	n.334-429G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000500

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000189

AC:

AN:

248552

Hom.:

AF XY:

0.000155

AC XY:

AN XY:

135204

show subpopulations

Gnomad AFR exome

AF:

0.000132

Gnomad AMR exome

AF:

0.000116

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000356

Gnomad OTH exome

AF:

0.000165

GnomAD4 exome

AF:

0.000424

AC:

620

AN:

1461706

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

313

AN XY:

727148

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.000534

Gnomad4 OTH exome

AF:

0.000331

GnomAD4 genome

AF:

0.000269

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000500

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000347

Hom.:

Bravo

AF:

0.000242

TwinsUK

AF:

0.00108

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.000463

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000173

AC:

EpiCase

AF:

0.000927

EpiControl

AF:

0.000237

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 21, 2022

The c.977C>T (p.A326V) alteration is located in exon 2 (coding exon 2) of the ATAD5 gene. This alteration results from a C to T substitution at nucleotide position 977, causing the alanine (A) at amino acid position 326 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.53

BayesDel_addAF

Benign

-0.035

BayesDel_noAF

Uncertain

0.060

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.32

Eigen

Pathogenic

0.84

Eigen_PC

Pathogenic

0.83

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.84

M_CAP

Benign

0.012

MetaRNN

Uncertain

0.58

MetaSVM

Benign

-0.69

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.0

REVEL

Benign

0.22

Sift

Pathogenic

0.0

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.68

MVP

0.35

MPC

0.32

ClinPred

0.13

GERP RS

5.9

Varity_R

0.28

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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