X-73213839-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_021963.4(NAP1L2):​c.654G>C​(p.Glu218Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000414 in 1,208,135 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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0000091 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.0000036 ( 0 hom. 2 hem. )

Consequence

NAP1L2
NM_021963.4 missense

Scores

17

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.31
Variant links:
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.035288393).
BP6
Variant X-73213839-C-G is Benign according to our data. Variant chrX-73213839-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2248648.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NAP1L2NM_021963.4 linkc.654G>C p.Glu218Asp missense_variant Exon 1 of 1 ENST00000373517.4 NP_068798.1 Q9ULW6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NAP1L2ENST00000373517.4 linkc.654G>C p.Glu218Asp missense_variant Exon 1 of 1 6 NM_021963.4 ENSP00000362616.3 Q9ULW6-1

Frequencies

GnomAD3 genomes
AF:
0.00000906
AC:
1
AN:
110378
Hom.:
0
Cov.:
22
AF XY:
0.0000307
AC XY:
1
AN XY:
32608
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000969
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:
0.00000364
AC:
4
AN:
1097757
Hom.:
0
Cov.:
32
AF XY:
0.00000551
AC XY:
2
AN XY:
363219
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:
0.00000475
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000906
AC:
1
AN:
110378
Hom.:
0
Cov.:
22
AF XY:
0.0000307
AC XY:
1
AN XY:
32608
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.0000969
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
Bravo
AF:
0.00000756

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Sep 01, 2021
Ambry Genetics
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.078
BayesDel_addAF
Benign
-0.46
T
BayesDel_noAF
Benign
-0.89
CADD
Benign
0.0070
DANN
Benign
0.31
DEOGEN2
Benign
0.0084
T
FATHMM_MKL
Benign
0.020
N
LIST_S2
Benign
0.27
T
M_CAP
Benign
0.00073
T
MetaRNN
Benign
0.035
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.060
N
PrimateAI
Benign
0.31
T
PROVEAN
Benign
0.0
N
REVEL
Benign
0.018
Sift
Benign
0.53
T
Sift4G
Benign
0.61
T
Polyphen
0.0
B
Vest4
0.096
MutPred
0.40
Loss of helix (P = 0.0558);
MVP
0.11
MPC
0.19
ClinPred
0.019
T
GERP RS
-6.0
Varity_R
0.060
gMVP
0.22

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: rs989511231; hg19: chrX-72433675; API