X-93672191-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004538.6(NAP1L3):​c.1114G>A​(p.Val372Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000146 in 1,098,224 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 7 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 0.000015 ( 0 hom. 7 hem. )

Consequence

NAP1L3
NM_004538.6 missense

Scores

1
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.2404997).
BS2
High Hemizygotes in GnomAdExome4 at 7 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAP1L3NM_004538.6 linkc.1114G>A p.Val372Met 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
NAP1L3ENST00000373079.4 linkc.1114G>A p.Val372Met missense_variant Exon 1 of 1 6 NM_004538.6 ENSP00000362171.3 Q99457
NAP1L3ENST00000475430.2 linkc.1093G>A p.Val365Met missense_variant Exon 2 of 2 2 ENSP00000476891.1 V9GYL6

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD3 exomes
AF:
0.0000218
AC:
4
AN:
183212
Hom.:
0
AF XY:
0.0000148
AC XY:
1
AN XY:
67710
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000489
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000146
AC:
16
AN:
1098224
Hom.:
0
Cov.:
31
AF XY:
0.0000193
AC XY:
7
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:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000166
Gnomad4 OTH exome
AF:
0.0000434
GnomAD4 genome
Cov.:
22
Bravo
AF:
0.00000756
ExAC
AF:
0.0000165
AC:
2
EpiCase
AF:
0.000109
EpiControl
AF:
0.000119

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 04, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1114G>A (p.V372M) alteration is located in exon 1 (coding exon 1) of the NAP1L3 gene. This alteration results from a G to A substitution at nucleotide position 1114, causing the valine (V) at amino acid position 372 to be replaced by a methionine (M). 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
Benign
0.11
BayesDel_addAF
Benign
-0.47
T
BayesDel_noAF
Benign
-0.80
CADD
Benign
15
DANN
Uncertain
0.99
DEOGEN2
Benign
0.091
T;T
FATHMM_MKL
Benign
0.48
N
LIST_S2
Benign
0.82
T;T
M_CAP
Benign
0.0031
T
MetaRNN
Benign
0.24
T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
1.9
L;.
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-2.3
N;.
REVEL
Benign
0.18
Sift
Benign
0.12
T;.
Sift4G
Benign
0.090
T;T
Polyphen
0.93
P;.
Vest4
0.072
MutPred
0.71
Loss of ubiquitination at K375 (P = 0.0811);.;
MVP
0.40
MPC
0.23
ClinPred
0.18
T
GERP RS
-2.8
Varity_R
0.063
gMVP
0.58

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.

Other links and lift over

dbSNP: rs758033690; hg19: chrX-92927190; API