17-30834235-A-C

Variant names:

• chr17-30834235-A-C
• rs139839085
• NM_024857.5:c.154A>C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_024857.5(ATAD5):​c.154A>C​(p.Arg52Arg) variant causes a synonymous change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000361 in 1,613,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00037 (0 hom.)
• Consequence: ATAD5 NM_024857.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 7.82

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]

ENSG00000265334 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 17-30834235-A-C is Benign according to our data. Variant chr17-30834235-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 3041965.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATAD5	NM_024857.5	c.154A>C	p.Arg52Arg	synonymous_variant	Exon 2 of 23	ENST00000321990.5	NP_079133.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATAD5	ENST00000321990.5	c.154A>C	p.Arg52Arg	synonymous_variant	Exon 2 of 23	1	NM_024857.5	ENSP00000313171.4
ATAD5	ENST00000578295.5	n.154A>C		non_coding_transcript_exon_variant	Exon 2 of 15	1		ENSP00000463102.1
ENSG00000265334	ENST00000580873.1	n.*90T>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.000282 AC: 43 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000458

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00124

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.000508 AC: 127 AN: 250058 Hom.: 0 AF XY: 0.000547 AC XY: 74 AN XY: 135310

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000758

Gnomad ASJ exome AF: 0.00189

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000892

Gnomad FIN exome AF: 0.000323

Gnomad NFE exome AF: 0.000344

Gnomad OTH exome AF: 0.00148

GnomAD4 exome AF: 0.000370 AC: 540 AN: 1460850 Hom.: 0 Cov.: 32 AF XY: 0.000376 AC XY: 273 AN XY: 726702

Gnomad4 AFR exome AF: 0.0000897

Gnomad4 AMR exome AF: 0.000606

Gnomad4 ASJ exome AF: 0.00184

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000872

Gnomad4 FIN exome AF: 0.000356

Gnomad4 NFE exome AF: 0.000281

Gnomad4 OTH exome AF: 0.000580

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152342 Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19 AN XY: 74506

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.000458

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00124

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.000947

Alfa AF: 0.000363 Hom.: 0

Bravo AF: 0.000230

Asia WGS AF: 0.000867 AC: 3 AN: 3476

EpiCase AF: 0.000545

EpiControl AF: 0.000771

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

Submissions by phenotype

ATAD5-related disorder Benign:1

May 17, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.77
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.6

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

Other links and lift over

dbSNP: rs139839085; hg19: chr17-29161253;