NM_021963.4:c.898G>A

Variant names:

• chrX-73213595-C-T
• NM_021963.4:c.898G>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_021963.4(NAP1L2):​c.898G>A​(p.Glu300Lys) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: NAP1L2 NM_021963.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58
• Publications: 0 publications found

Genes affected

NAP1L2 (HGNC:7638): (nucleosome assembly protein 1 like 2) The protein encoded by this intronless gene is a member of the nucleosome assembly protein (NAP) family. The encoded protein represents a class of tissue-specific factors that interact with chromatin to regulate neuronal cell proliferation. [provided by RefSeq, Jan 2011]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.29364923).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021963.4. 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
	NAP1L2	NM_021963.4	MANE Select	c.898G>A	p.Glu300Lys	missense	Exon 1 of 1	NP_068798.1	Q9ULW6-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAP1L2	ENST00000373517.4	TSL:6 MANE Select	c.898G>A	p.Glu300Lys	missense	Exon 1 of 1	ENSP00000362616.3	Q9ULW6-1
	NAP1L2	ENST00000861013.1		c.898G>A	p.Glu300Lys	missense	Exon 2 of 2	ENSP00000531072.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 23

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	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
FATHMM_MKL	Benign	0.44	N
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.58	N
PhyloP100		1.6
PrimateAI	Uncertain	0.58	T
PROVEAN	Benign	-0.44	N
REVEL	Benign	0.16
Sift	Benign	0.24	T
Sift4G	Benign	0.11	T
Polyphen		0.98	D
Vest4		0.20
MutPred		0.57		Gain of methylation at E300 (P = 0.0051)
MVP		0.23
MPC		0.24
ClinPred		0.57	D
GERP RS		2.9
Varity_R		0.29
gMVP		0.61
Mutation Taster		=90/10	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: chrX-72433431; COSMIC: COSV65172427;