chr17-30834340-C-T

Variant names:

• chr17-30834340-C-T
• rs3816780
• NM_024857.5:c.259C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_024857.5(ATAD5):​c.259C>T​(p.Pro87Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.121 in 1,609,988 control chromosomes in the GnomAD database, including 13,291 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P87A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.13 (1452 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11839 hom.)
• Consequence: ATAD5 NM_024857.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.100
• Publications: 39 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0027531087).
• BP6: Variant 17-30834340-C-T is Benign according to our data. Variant chr17-30834340-C-T is described in ClinVar as Benign. ClinVar VariationId is 3059655.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024857.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATAD5	NM_024857.5	MANE Select	c.259C>T	p.Pro87Ser	missense	Exon 2 of 23	NP_079133.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATAD5	ENST00000321990.5	TSL:1 MANE Select	c.259C>T	p.Pro87Ser	missense	Exon 2 of 23	ENSP00000313171.4	Q96QE3-1
	ATAD5	ENST00000578295.5	TSL:1	n.259C>T		non_coding_transcript_exon	Exon 2 of 15	ENSP00000463102.1	A0A075B754
	ATAD5	ENST00000933271.1		c.259C>T	p.Pro87Ser	missense	Exon 2 of 23	ENSP00000603330.1

Frequencies

GnomAD3 genomes AF: 0.133 AC: 19959 AN: 150250 Hom.: 1442 Cov.: 32

Gnomad AFR AF: 0.166

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0875

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.244

Gnomad FIN AF: 0.0884

Gnomad MID AF: 0.0980

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.124

GnomAD2 exomes AF: 0.137 AC: 34064 AN: 249084 AF XY: 0.138

Gnomad AFR exome AF: 0.166

Gnomad AMR exome AF: 0.176

Gnomad ASJ exome AF: 0.0871

Gnomad EAS exome AF: 0.123

Gnomad FIN exome AF: 0.0856

Gnomad NFE exome AF: 0.109

Gnomad OTH exome AF: 0.121

GnomAD4 exome AF: 0.119 AC: 174395 AN: 1459614 Hom.: 11839 Cov.: 32 AF XY: 0.122 AC XY: 88744 AN XY: 726012

African (AFR) AF: 0.165 AC: 5512 AN: 33376

American (AMR) AF: 0.173 AC: 7664 AN: 44276

Ashkenazi Jewish (ASJ) AF: 0.0890 AC: 2319 AN: 26064

East Asian (EAS) AF: 0.161 AC: 6376 AN: 39638

South Asian (SAS) AF: 0.243 AC: 20776 AN: 85630

European-Finnish (FIN) AF: 0.0879 AC: 4690 AN: 53384

Middle Eastern (MID) AF: 0.109 AC: 630 AN: 5758

European-Non Finnish (NFE) AF: 0.107 AC: 118965 AN: 1111186

Other (OTH) AF: 0.124 AC: 7463 AN: 60302

GnomAD4 genome AF: 0.133 AC: 20011 AN: 150374 Hom.: 1452 Cov.: 32 AF XY: 0.134 AC XY: 9875 AN XY: 73484

African (AFR) AF: 0.167 AC: 6815 AN: 40930

American (AMR) AF: 0.164 AC: 2482 AN: 15110

Ashkenazi Jewish (ASJ) AF: 0.0875 AC: 300 AN: 3428

East Asian (EAS) AF: 0.135 AC: 680 AN: 5044

South Asian (SAS) AF: 0.246 AC: 1168 AN: 4748

European-Finnish (FIN) AF: 0.0884 AC: 923 AN: 10438

Middle Eastern (MID) AF: 0.0938 AC: 27 AN: 288

European-Non Finnish (NFE) AF: 0.107 AC: 7205 AN: 67394

Other (OTH) AF: 0.126 AC: 264 AN: 2090

Alfa AF: 0.114 Hom.: 4759

Bravo AF: 0.136

TwinsUK AF: 0.108 AC: 402

ALSPAC AF: 0.105 AC: 403

ESP6500AA AF: 0.166 AC: 730

ESP6500EA AF: 0.105 AC: 902

ExAC AF: 0.140 AC: 16974

Asia WGS AF: 0.195 AC: 678 AN: 3478

EpiCase AF: 0.103

EpiControl AF: 0.103

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	ATAD5-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.058
BayesDel_addAF	Benign	-0.79	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.73
DANN	Benign	0.61
DEOGEN2	Benign	0.028	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0076	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.0028	T
MetaSVM	Benign	-0.96	T
MutationAssessor	Benign	-2.3	N
PhyloP100		-0.10
PrimateAI	Benign	0.28	T
PROVEAN	Benign	1.4	N
REVEL	Benign	0.043
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.036
MPC		0.070
ClinPred		0.0030	T
GERP RS		1.4
Varity_R		0.025
gMVP		0.043
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3816780; hg19: chr17-29161358; COSMIC: COSV58972907; COSMIC: COSV58972907;