NM_024857.5:c.418G>A

Variant names:

• chr17-30834499-G-A
• rs147909444
• NM_024857.5:c.418G>A

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_Strong BP6 BS2

The NM_024857.5(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. 14/22 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 NM_024857.5 missense
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: 3.08
• Publications: 9 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 -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 VariationId is 3043100.Status of the report is no_assertion_criteria_provided, 0 stars.
• BS2: High AC in GnomAd4 at 336 AD gene.

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.418G>A	p.Asp140Asn	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.418G>A	p.Asp140Asn	missense	Exon 2 of 23	ENSP00000313171.4	Q96QE3-1
	ATAD5	ENST00000578295.5	TSL:1	n.418G>A		non_coding_transcript_exon	Exon 2 of 15	ENSP00000463102.1	A0A075B754
	ATAD5	ENST00000933271.1		c.418G>A	p.Asp140Asn	missense	Exon 2 of 23	ENSP00000603330.1

Frequencies

GnomAD3 genomes AF: 0.00221 AC: 336 AN: 152152 Hom.: 1 Cov.: 32

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

GnomAD2 exomes AF: 0.00252 AC: 568 AN: 224986 AF XY: 0.00240

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 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.: 7 Cov.: 34 AF XY: 0.00332 AC XY: 2366 AN XY: 712346

African (AFR) AF: 0.000602 AC: 19 AN: 31548

American (AMR) AF: 0.000408 AC: 15 AN: 36770

Ashkenazi Jewish (ASJ) AF: 0.000121 AC: 3 AN: 24838

East Asian (EAS) AF: 0.0000759 AC: 3 AN: 39532

South Asian (SAS) AF: 0.000224 AC: 18 AN: 80276

European-Finnish (FIN) AF: 0.00479 AC: 250 AN: 52242

Middle Eastern (MID) AF: 0.000355 AC: 2 AN: 5628

European-Non Finnish (NFE) AF: 0.00408 AC: 4494 AN: 1102732

Other (OTH) AF: 0.00211 AC: 125 AN: 59158

GnomAD4 genome AF: 0.00221 AC: 336 AN: 152270 Hom.: 1 Cov.: 32 AF XY: 0.00189 AC XY: 141 AN XY: 74444

African (AFR) AF: 0.000602 AC: 25 AN: 41560

American (AMR) AF: 0.000589 AC: 9 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00434 AC: 46 AN: 10608

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00371 AC: 252 AN: 68014

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00321 Hom.: 0

Bravo AF: 0.00192

TwinsUK AF: 0.00324 AC: 12

ALSPAC AF: 0.00441 AC: 17

ESP6500AA AF: 0.00159 AC: 7

ESP6500EA AF: 0.00419 AC: 36

ExAC AF: 0.00277 AC: 336

ClinVar

ClinVar submissions

Significance: Likely 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	0.086
BayesDel_addAF	Benign	-0.58	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	20
DANN	Benign	0.79
DEOGEN2	Benign	0.26	T
Eigen	Uncertain	0.54
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.0080	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.1
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.14
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.36	T
Polyphen		1.0	D
Vest4		0.18
MVP		0.37
MPC		0.25
ClinPred		0.032	T
GERP RS		5.8
Varity_R		0.15
gMVP		0.12
Mutation Taster		=98/2	polymorphism

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: rs147909444; hg19: chr17-29161517; COSMIC: COSV58974538; COSMIC: COSV58974538;