NM_014109.4:c.3909G>T

Variant names:

• chr8-123325986-C-A
• NM_014109.4:c.3909G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_014109.4(ATAD2):​c.3909G>T​(p.Gln1303His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q1303R) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: ATAD2 NM_014109.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.171
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26001036).

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.3909G>T	p.Gln1303His	missense	Exon 26 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.3909G>T	p.Gln1303His	missense	Exon 26 of 28	ENSP00000287394.5	Q6PL18-1
	ATAD2	ENST00000521903.5	TSL:1	c.1863G>T	p.Gln621His	missense	Exon 27 of 29	ENSP00000429213.1	A0A0B4J211
	ATAD2	ENST00000519124.5	TSL:1	n.*3719G>T		non_coding_transcript_exon	Exon 26 of 28	ENSP00000429617.1	E5RHW7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.29
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	17
DANN	Uncertain	1.0
DEOGEN2	Benign	0.099	T
Eigen	Benign	0.088
Eigen_PC	Benign	0.060
FATHMM_MKL	Benign	0.67	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.30	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.17
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-1.8	N
REVEL	Uncertain	0.39
Sift	Benign	0.10	T
Sift4G	Benign	0.099	T
Polyphen		1.0	D
Vest4		0.34
MutPred		0.19		Loss of disorder (P = 0.1154)
MVP		0.88
MPC		0.76
ClinPred		0.88	D
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.8
Varity_R		0.047
gMVP		0.35
Mutation Taster		=77/23	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

hg19: chr8-124338226; COSMIC: COSV54884371;