X-93671927-C-T

Variant names:

• chrX-93671927-C-T
• rs778586248
• NM_004538.6:c.1378G>A

Variant summary

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

The NM_004538.6(NAP1L3):​c.1378G>A​(p.Ala460Thr) variant causes a missense change. The variant allele was found at a frequency of 0.00000896 in 111,565 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. 12/21 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. A460S) has been classified as Uncertain significance.

• Frequency: Genomes: 𝑓 0.0000090 (0 hom., 0 hem., cov: 22)
• Consequence: NAP1L3 NM_004538.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85
• Publications: 1 publications found

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

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=0.20023453).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004538.6. 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
	NAP1L3	NM_004538.6	MANE Select	c.1378G>A	p.Ala460Thr	missense	Exon 1 of 1	NP_004529.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAP1L3	ENST00000373079.4	TSL:6 MANE Select	c.1378G>A	p.Ala460Thr	missense	Exon 1 of 1	ENSP00000362171.3	Q99457
	NAP1L3	ENST00000475430.2	TSL:2	c.1357G>A	p.Ala453Thr	missense	Exon 2 of 2	ENSP00000476891.1	V9GYL6

Frequencies

GnomAD3 genomes AF: 0.00000896 AC: 1 AN: 111565 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.0000188

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 30

GnomAD4 genome AF: 0.00000896 AC: 1 AN: 111565 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33737

African (AFR) AF: 0.00 AC: 0 AN: 30675

American (AMR) AF: 0.00 AC: 0 AN: 10455

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2646

East Asian (EAS) AF: 0.00 AC: 0 AN: 3544

South Asian (SAS) AF: 0.00 AC: 0 AN: 2636

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6037

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 238

European-Non Finnish (NFE) AF: 0.0000188 AC: 1 AN: 53139

Other (OTH) AF: 0.00 AC: 0 AN: 1511

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.20
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.015	T
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.73	T
M_CAP	Benign	0.0086	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		3.8
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.11
Sift	Benign	0.087	T
Sift4G	Benign	0.069	T
Polyphen		1.0	D
Vest4		0.17
MutPred		0.40		Gain of phosphorylation at A460 (P = 0.0323)
MVP		0.77
MPC		0.78
ClinPred		0.96	D
GERP RS		3.4
Varity_R		0.39
gMVP		0.099
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: rs778586248; hg19: chrX-92926926;