X-73213352-A-T

Variant names:

• chrX-73213352-A-T
• rs1474553943
• NM_021963.4:c.1141T>A

Variant summary

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

The NM_021963.4(NAP1L2):​c.1141T>A​(p.Ser381Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000911 in 1,097,909 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S381A) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 23)
  • Exomes 𝑓: 9.1e-7 (0 hom. 0 hem.)
• Consequence: NAP1L2 NM_021963.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.776
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10248923).

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.1141T>A	p.Ser381Thr	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.1141T>A	p.Ser381Thr	missense	Exon 1 of 1	ENSP00000362616.3	Q9ULW6-1
	NAP1L2	ENST00000861013.1		c.1141T>A	p.Ser381Thr	missense	Exon 2 of 2	ENSP00000531072.1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome AF: 9.11e-7 AC: 1 AN: 1097909 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 363277

African (AFR) AF: 0.00 AC: 0 AN: 26398

American (AMR) AF: 0.00 AC: 0 AN: 35202

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19380

East Asian (EAS) AF: 0.0000331 AC: 1 AN: 30195

South Asian (SAS) AF: 0.00 AC: 0 AN: 54130

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4135

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841857

Other (OTH) AF: 0.00 AC: 0 AN: 46082

GnomAD4 genome Cov.: 23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.1
DANN	Benign	0.70
DEOGEN2	Benign	0.015	T
FATHMM_MKL	Benign	0.12	N
LIST_S2	Benign	0.25	T
M_CAP	Benign	0.0023	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.68	N
PhyloP100		0.78
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-0.81	N
REVEL	Benign	0.029
Sift	Benign	0.51	T
Sift4G	Benign	0.54	T
Polyphen		0.50	P
Vest4		0.086
MutPred		0.34		Loss of disorder (P = 0.0839)
MVP		0.29
MPC		0.25
ClinPred		0.19	T
GERP RS		3.0
Varity_R		0.15
gMVP		0.087
Mutation Taster		=96/4	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: rs1474553943; hg19: chrX-72433188; COSMIC: COSV100999217;