NM_017552.4:c.3911C>G

Variant names:

• chr2-23757585-G-C
• rs372015732
• NM_017552.4:c.3911C>G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017552.4(ATAD2B):​c.3911C>G​(p.Ser1304Cys) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,460,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict 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: 6.8e-7 (0 hom.)
• Consequence: ATAD2B NM_017552.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.82

Genes affected

ATAD2B (HGNC:29230): (ATPase family AAA domain containing 2B) The protein encoded by this gene belongs to the AAA ATPase family. This family member includes an N-terminal bromodomain. It has been found to be localized to the nucleus, partly to replication sites, consistent with a chromatin-related function. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Jul 2014]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.18802434).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ATAD2B	NM_017552.4	c.3911C>G	p.Ser1304Cys	missense_variant	Exon 25 of 28	ENST00000238789.10	NP_060022.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ATAD2B	ENST00000238789.10	c.3911C>G	p.Ser1304Cys	missense_variant	Exon 25 of 28	5	NM_017552.4	ENSP00000238789.5
ATAD2B	ENST00000381024.4	c.1736C>G	p.Ser579Cys	missense_variant	Exon 9 of 12	1		ENSP00000370412.4
ATAD2B	ENST00000474583.5	n.3056C>G		non_coding_transcript_exon_variant	Exon 16 of 19	2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460826 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 726662

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Uncertain	0.097	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	22
DANN	Benign	0.97
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.43
FATHMM_MKL	Benign	0.67	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	0.017	D
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.2	N
REVEL	Uncertain	0.32
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.054	T
Vest4		0.18
MutPred		0.22		Loss of phosphorylation at S1304 (P = 0.0354);
MVP		0.70
MPC		0.91
ClinPred		0.79	D
GERP RS		4.9
gMVP		0.26

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

Publications

LitVar

Other links and lift over

dbSNP: rs372015732; hg19: chr2-23980455;