NM_017552.4:c.3965C>T

Variant names:

• chr2-23757531-G-A
• rs941099886
• NM_017552.4:c.3965C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_017552.4(ATAD2B):​c.3965C>T​(p.Thr1322Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000628 in 1,592,518 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T1322A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000042 (0 hom.)
• Consequence: ATAD2B NM_017552.4 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.150
• Publications: 0 publications found

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

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.044575006).
• BP6: Variant 2-23757531-G-A is Benign according to our data. Variant chr2-23757531-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3130673.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAdExome4 at 6 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017552.4. 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
	ATAD2B	NM_017552.4	MANE Select	c.3965C>T	p.Thr1322Ile	missense	Exon 25 of 28	NP_060022.2	Q9ULI0-1
	ATAD2B	NM_001354107.2		c.3992C>T	p.Thr1331Ile	missense	Exon 26 of 29	NP_001341036.1
	ATAD2B	NM_001242338.3		c.3950C>T	p.Thr1317Ile	missense	Exon 25 of 28	NP_001229267.2	Q9ULI0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ATAD2B	ENST00000238789.10	TSL:5 MANE Select	c.3965C>T	p.Thr1322Ile	missense	Exon 25 of 28	ENSP00000238789.5	Q9ULI0-1
	ATAD2B	ENST00000381024.4	TSL:1	c.1790C>T	p.Thr597Ile	missense	Exon 9 of 12	ENSP00000370412.4	H7BYF1
	ATAD2B	ENST00000925212.1		c.3950C>T	p.Thr1317Ile	missense	Exon 25 of 28	ENSP00000595271.1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152120 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000417 AC: 6 AN: 1440398 Hom.: 0 Cov.: 31 AF XY: 0.00000279 AC XY: 2 AN XY: 715772

African (AFR) AF: 0.00 AC: 0 AN: 31918

American (AMR) AF: 0.0000252 AC: 1 AN: 39702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24934

East Asian (EAS) AF: 0.00 AC: 0 AN: 39490

South Asian (SAS) AF: 0.0000367 AC: 3 AN: 81728

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52872

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5638

European-Non Finnish (NFE) AF: 0.00000181 AC: 2 AN: 1104664

Other (OTH) AF: 0.00 AC: 0 AN: 59452

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152120 Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2 AN XY: 74292

African (AFR) AF: 0.00 AC: 0 AN: 41412

American (AMR) AF: 0.000262 AC: 4 AN: 15276

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5196

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000285 Hom.: 0

Bravo AF: 0.0000302

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.082
BayesDel_addAF	Benign	-0.086	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	2.6
DANN	Benign	0.85
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.071	N
M_CAP	Benign	0.065	D
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.61	T
PhyloP100		-0.15
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-0.89	N
REVEL	Benign	0.29
Sift	Benign	0.21	T
Sift4G	Benign	0.29	T
Vest4		0.044
MutPred		0.21		Loss of phosphorylation at T1322 (P = 0.0146)
MVP		0.55
MPC		0.53
ClinPred		0.045	T
GERP RS		-3.9
gMVP		0.054
Mutation Taster		=99/1	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: rs941099886; hg19: chr2-23980401;