dbSNP rs758033690: NAP1L3:p.Val372Leu (chrX-93672191-C-A) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_004538.6(NAP1L3):c.1114G>T(p.Val372Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000546 in 1,098,224 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in Lovd as Likely benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V372M) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., 0 hem., cov: 22)

Exomes 𝑓: 0.0000055 ( 0 hom. 3 hem. )

Failed GnomAD Quality Control

Consequence

NAP1L3
NM_004538.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.189

Variant links:

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]

NAP1L3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.19779253).

BP6

Variant X-93672191-C-A is Benign according to our data. Variant chrX-93672191-C-A is described in Lovd as [Likely_benign].

BS2

High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAP1L3	NM_004538.6 link	c.1114G>T	p.Val372Leu	missense_variant	Exon 1 of 1	ENST00000373079.4	NP_004529.2	Q99457Q8IYV1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAP1L3	ENST00000373079.4 link	c.1114G>T	p.Val372Leu	missense_variant	Exon 1 of 1	6	NM_004538.6	ENSP00000362171.3		Q99457
NAP1L3	ENST00000475430.2 link	c.1093G>T	p.Val365Leu	missense_variant	Exon 2 of 2	2		ENSP00000476891.1		V9GYL6

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

111519

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33699

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000546

AC:

AN:

1098224

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

363580

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000739

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.0000217

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

111519

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33699

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.6

DANN

Benign

0.71

DEOGEN2

Benign

0.042

T;T

FATHMM_MKL

Benign

0.59

LIST_S2

Benign

0.77

T;T

M_CAP

Benign

0.0027

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;.

PrimateAI

Benign

0.36

PROVEAN

Benign

-2.1

N;.

REVEL

Benign

0.12

Sift

Benign

0.34

T;.

Sift4G

Benign

0.44

T;T

Polyphen

0.44

B;.

Vest4

0.077

MutPred

0.71

Loss of methylation at K375 (P = 0.0831);.;

MVP

0.40

MPC

0.22

ClinPred

0.18

GERP RS

-2.8

Varity_R

0.093

gMVP

0.60

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over