chr8-123328575-C-T

Variant names:

• chr8-123328575-C-T
• rs771461342
• NM_014109.4:c.3483G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_014109.4(ATAD2):​c.3483G>A​(p.Gln1161Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000146 in 1,365,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: ATAD2 NM_014109.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.204
• Publications: 0 publications found

Genes affected

ATAD2 (HGNC:30123): (ATPase family AAA domain containing 2) A large family of ATPases has been described, whose key feature is that they share a conserved region of about 220 amino acids that contains an ATP-binding site. The proteins that belong to this family either contain one or two AAA (ATPases Associated with diverse cellular Activities) domains. AAA family proteins often perform chaperone-like functions that assist in the assembly, operation, or disassembly of protein complexes. The protein encoded by this gene contains two AAA domains, as well as a bromodomain. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP7: Synonymous conserved (PhyloP=0.204 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014109.4. 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
	ATAD2	NM_014109.4	MANE Select	c.3483G>A	p.Gln1161Gln	synonymous	Exon 25 of 28	NP_054828.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATAD2	ENST00000287394.10	TSL:1 MANE Select	c.3483G>A	p.Gln1161Gln	synonymous	Exon 25 of 28	ENSP00000287394.5	Q6PL18-1
	ATAD2	ENST00000521903.5	TSL:1	c.1437G>A	p.Gln479Gln	synonymous	Exon 26 of 29	ENSP00000429213.1	A0A0B4J211
	ATAD2	ENST00000519124.5	TSL:1	n.*3293G>A		non_coding_transcript_exon	Exon 25 of 28	ENSP00000429617.1	E5RHW7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000215 AC: 4 AN: 185734 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: 0.0000107

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000146 AC: 2 AN: 1365878 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 671032

African (AFR) AF: 0.00 AC: 0 AN: 29872

American (AMR) AF: 0.00 AC: 0 AN: 27612

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21844

East Asian (EAS) AF: 0.00 AC: 0 AN: 37764

South Asian (SAS) AF: 0.0000146 AC: 1 AN: 68556

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50886

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5404

European-Non Finnish (NFE) AF: 9.37e-7 AC: 1 AN: 1067654

Other (OTH) AF: 0.00 AC: 0 AN: 56286

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	5.3
DANN	Benign	0.53
PhyloP100		0.20

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: rs771461342; hg19: chr8-124340815;