X-93672064-A-C

Variant names:

• chrX-93672064-A-C
• NM_004538.6:c.1241T>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004538.6(NAP1L3):​c.1241T>G​(p.Val414Gly) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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: 22)
• Consequence: NAP1L3 NM_004538.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.90

Genes affected

NAP1L3 (HGNC:7639): (nucleosome assembly protein 1 like 3) This gene is intronless and encodes a member of the nucleosome assembly protein (NAP) family. This gene is linked closely to a region of genes responsible for several X-linked cognitive disability syndromes. [provided by RefSeq, Dec 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.38504457).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAP1L3	NM_004538.6	c.1241T>G	p.Val414Gly	missense_variant	Exon 1 of 1	ENST00000373079.4	NP_004529.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAP1L3	ENST00000373079.4	c.1241T>G	p.Val414Gly	missense_variant	Exon 1 of 1	6	NM_004538.6	ENSP00000362171.3
NAP1L3	ENST00000475430.2	c.1220T>G	p.Val407Gly	missense_variant	Exon 2 of 2	2		ENSP00000476891.1

Frequencies

GnomAD3 genomes Cov.: 22

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 22

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 12, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1241T>G (p.V414G) alteration is located in exon 1 (coding exon 1) of the NAP1L3 gene. This alteration results from a T to G substitution at nucleotide position 1241, causing the valine (V) at amino acid position 414 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.53
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.034	T;T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.39	T;T
M_CAP	Benign	0.022	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Pathogenic	3.0	M;.
PrimateAI	Benign	0.28	T
PROVEAN	Pathogenic	-6.2	D;.
REVEL	Benign	0.22
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.0020	D;D
Polyphen		0.97	D;.
Vest4		0.23
MutPred		0.76		Loss of stability (P = 0.0162);.;
MVP		0.46
MPC		0.89
ClinPred		0.99	D
GERP RS		2.3
Varity_R		0.93
gMVP		0.82

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-92927063;