rs3816780

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr17-30834340-C-A
• chr17-30834340-C-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_024857.5(ATAD5):​c.259C>A​(p.Pro87Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000994 in 1,610,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. 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 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: ATAD5 NM_024857.5 missense
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.03821948).
• BS2: High AC in GnomAdExome4 at 14 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.259C>A	p.Pro87Thr	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>A	p.Pro87Thr	missense	Exon 2 of 23	ENSP00000313171.4	Q96QE3-1
	ATAD5	ENST00000578295.5	TSL:1	n.259C>A		non_coding_transcript_exon	Exon 2 of 15	ENSP00000463102.1	A0A075B754
	ATAD5	ENST00000933271.1		c.259C>A	p.Pro87Thr	missense	Exon 2 of 23	ENSP00000603330.1

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150284 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000297

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000401 AC: 1 AN: 249084 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000885

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000959 AC: 14 AN: 1459926 Hom.: 0 Cov.: 32 AF XY: 0.00000689 AC XY: 5 AN XY: 726152

African (AFR) AF: 0.00 AC: 0 AN: 33388

American (AMR) AF: 0.00 AC: 0 AN: 44300

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39640

South Asian (SAS) AF: 0.00 AC: 0 AN: 85672

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1111402

Other (OTH) AF: 0.00 AC: 0 AN: 60312

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150284 Hom.: 0 Cov.: 32 AF XY: 0.0000136 AC XY: 1 AN XY: 73382

African (AFR) AF: 0.00 AC: 0 AN: 40826

American (AMR) AF: 0.00 AC: 0 AN: 15092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3428

East Asian (EAS) AF: 0.00 AC: 0 AN: 5056

South Asian (SAS) AF: 0.00 AC: 0 AN: 4756

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.0000297 AC: 2 AN: 67406

Other (OTH) AF: 0.00 AC: 0 AN: 2070

Alfa AF: 0.00 Hom.: 4759

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.053
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.66
CADD	Benign	0.53
DANN	Benign	0.59
DEOGEN2	Benign	0.026	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.059	N
LIST_S2	Benign	0.32	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.038	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.10
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.39	N
REVEL	Benign	0.024
Sift	Uncertain	0.0060	D
Sift4G	Benign	0.10	T
Polyphen		0.0	B
Vest4		0.098
MutPred		0.14		Gain of phosphorylation at P87 (P = 0.0996)
MVP		0.043
MPC		0.078
ClinPred		0.032	T
GERP RS		1.4
Varity_R		0.043
gMVP		0.056
Mutation Taster		=100/0	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: rs3816780; hg19: chr17-29161358;