rs17826219

Variant names:

• chr17-30834827-G-A
• rs17826219
• NM_024857.5:c.746G>A

Your query was ambiguous. Multiple possible variants found:

• chr17-30834827-G-A
• chr17-30834827-G-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.746G>A​(p.Arg249Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 1,613,402 control chromosomes in the GnomAD database, including 12,300 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).

• Frequency:
  • Genomes: 𝑓 0.11 (955 hom., cov: 32)
  • Exomes 𝑓: 0.12 (11345 hom.)
• Consequence: ATAD5 NM_024857.5 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 2.47
• Publications: 27 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=0.0044242144).
• BP6: Variant 17-30834827-G-A is Benign according to our data. Variant chr17-30834827-G-A is described in ClinVar as Benign. ClinVar VariationId is 3059306.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.231 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.746G>A	p.Arg249Lys	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.746G>A	p.Arg249Lys	missense	Exon 2 of 23	ENSP00000313171.4	Q96QE3-1
	ATAD5	ENST00000578295.5	TSL:1	n.746G>A		non_coding_transcript_exon	Exon 2 of 15	ENSP00000463102.1	A0A075B754
	ATAD5	ENST00000933271.1		c.746G>A	p.Arg249Lys	missense	Exon 2 of 23	ENSP00000603330.1

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15959 AN: 152106 Hom.: 950 Cov.: 32

Gnomad AFR AF: 0.0719

Gnomad AMI AF: 0.163

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.0864

Gnomad EAS AF: 0.132

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.0872

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.104

GnomAD2 exomes AF: 0.130 AC: 32406 AN: 250168 AF XY: 0.133

Gnomad AFR exome AF: 0.0699

Gnomad AMR exome AF: 0.171

Gnomad ASJ exome AF: 0.0866

Gnomad EAS exome AF: 0.123

Gnomad FIN exome AF: 0.0856

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.117 AC: 170634 AN: 1461178 Hom.: 11345 Cov.: 34 AF XY: 0.120 AC XY: 87216 AN XY: 726862

African (AFR) AF: 0.0707 AC: 2365 AN: 33472

American (AMR) AF: 0.168 AC: 7478 AN: 44624

Ashkenazi Jewish (ASJ) AF: 0.0888 AC: 2319 AN: 26114

East Asian (EAS) AF: 0.161 AC: 6381 AN: 39680

South Asian (SAS) AF: 0.242 AC: 20836 AN: 86040

European-Finnish (FIN) AF: 0.0879 AC: 4693 AN: 53410

Middle Eastern (MID) AF: 0.103 AC: 591 AN: 5764

European-Non Finnish (NFE) AF: 0.107 AC: 118901 AN: 1111706

Other (OTH) AF: 0.117 AC: 7070 AN: 60368

GnomAD4 genome AF: 0.105 AC: 15993 AN: 152224 Hom.: 955 Cov.: 32 AF XY: 0.107 AC XY: 7976 AN XY: 74422

African (AFR) AF: 0.0720 AC: 2991 AN: 41526

American (AMR) AF: 0.153 AC: 2337 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0864 AC: 300 AN: 3472

East Asian (EAS) AF: 0.132 AC: 686 AN: 5190

South Asian (SAS) AF: 0.242 AC: 1169 AN: 4826

European-Finnish (FIN) AF: 0.0872 AC: 924 AN: 10602

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7187 AN: 68006

Other (OTH) AF: 0.107 AC: 225 AN: 2110

Alfa AF: 0.107 Hom.: 2383

Bravo AF: 0.106

TwinsUK AF: 0.108 AC: 401

ALSPAC AF: 0.104 AC: 401

ESP6500AA AF: 0.0736 AC: 324

ESP6500EA AF: 0.104 AC: 895

ExAC AF: 0.131 AC: 15919

Asia WGS AF: 0.190 AC: 660 AN: 3478

EpiCase AF: 0.102

EpiControl AF: 0.102

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	0.079
BayesDel_addAF	Benign	-0.71	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.1
DANN	Benign	0.58
DEOGEN2	Benign	0.075	T
Eigen	Benign	-0.58
Eigen_PC	Benign	-0.58
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.29	T
MetaRNN	Benign	0.0044	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		2.5
PrimateAI	Benign	0.21	T
PROVEAN	Benign	-0.83	N
REVEL	Benign	0.044
Sift	Benign	0.17	T
Sift4G	Benign	0.84	T
Polyphen		0.16	B
Vest4		0.0070
MPC		0.071
ClinPred		0.0082	T
GERP RS		3.3
Varity_R		0.065
gMVP		0.093
Mutation Taster		=98/2	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: rs17826219; hg19: chr17-29161845; COSMIC: COSV58972918; COSMIC: COSV58972918;