rs761743290

Variant names:

• chrX-73213969-C-G
• rs761743290
• NM_021963.4:c.524G>C

Your query was ambiguous. Multiple possible variants found:

• chrX-73213969-C-G
• chrX-73213969-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_021963.4(NAP1L2):​c.524G>C​(p.Cys175Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000273 in 1,098,043 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. 15/21 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. C175Y) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 22)
  • Exomes 𝑓: 0.0000027 (0 hom. 0 hem.)
• Consequence: NAP1L2 NM_021963.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.603
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03499481).

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.524G>C	p.Cys175Ser	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.524G>C	p.Cys175Ser	missense	Exon 1 of 1	ENSP00000362616.3	Q9ULW6-1
	NAP1L2	ENST00000861013.1		c.524G>C	p.Cys175Ser	missense	Exon 2 of 2	ENSP00000531072.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome AF: 0.00000273 AC: 3 AN: 1098043 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 363405

African (AFR) AF: 0.00 AC: 0 AN: 26400

American (AMR) AF: 0.00 AC: 0 AN: 35207

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 30203

South Asian (SAS) AF: 0.00 AC: 0 AN: 54132

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40506

Middle Eastern (MID) AF: 0.000242 AC: 1 AN: 4136

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 841985

Other (OTH) AF: 0.0000434 AC: 2 AN: 46092

GnomAD4 genome Cov.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.082
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.14
DANN	Benign	0.25
DEOGEN2	Benign	0.0052	T
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.093	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.080	N
PhyloP100		-0.60
PrimateAI	Benign	0.35	T
PROVEAN	Benign	1.2	N
REVEL	Benign	0.025
Sift	Benign	0.35	T
Sift4G	Benign	0.42	T
Polyphen		0.0	B
Vest4		0.098
MutPred		0.37		Gain of phosphorylation at C175 (P = 0.0022)
MVP		0.043
MPC		0.27
ClinPred		0.16	T
GERP RS		1.7
Varity_R		0.089
gMVP		0.054
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: rs761743290; hg19: chrX-72433805;