Genetic Variant NM_004538.6:c.830T>C (chrX-93672475-A-G) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_004538.6(NAP1L3):c.830T>C(p.Val277Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000141 in 1,209,490 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 5 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000045 ( 0 hom., 2 hem., cov: 22)

Exomes 𝑓: 0.000011 ( 0 hom. 3 hem. )

Consequence

NAP1L3
NM_004538.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.647

Publications

0 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.07025483).

BS2

High Hemizygotes in GnomAd4 at 2 gene

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.830T>C	p.Val277Ala	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.830T>C	p.Val277Ala	missense	Exon 1 of 1	ENSP00000362171.3	Q99457
	NAP1L3	ENST00000475430.2	TSL:2	c.809T>C	p.Val270Ala	missense	Exon 2 of 2	ENSP00000476891.1	V9GYL6

Frequencies

GnomAD3 genomes

AF:

0.0000449

AC:

AN:

111454

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000326

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:

0.0000754

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000109

AC:

AN:

183049

AF XY:

0.0000148

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000245

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000109

AC:

AN:

1098036

Hom.:

Cov.:

AF XY:

0.00000826

AC XY:

AN XY:

363400

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26397

American (AMR)

AF:

0.00

AC:

AN:

35193

Ashkenazi Jewish (ASJ)

AF:

0.0000516

AC:

AN:

19374

East Asian (EAS)

AF:

0.00

AC:

AN:

30205

South Asian (SAS)

AF:

0.00

AC:

AN:

54142

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40385

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4135

European-Non Finnish (NFE)

AF:

0.0000131

AC:

AN:

842111

Other (OTH)

AF:

0.00

AC:

AN:

46094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000449

AC:

AN:

111454

Hom.:

Cov.:

AF XY:

0.0000595

AC XY:

AN XY:

33632

show subpopulations

African (AFR)

AF:

0.0000326

AC:

AN:

30633

American (AMR)

AF:

0.00

AC:

AN:

10519

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2644

East Asian (EAS)

AF:

0.00

AC:

AN:

3526

South Asian (SAS)

AF:

0.00

AC:

AN:

2601

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6050

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.0000754

AC:

AN:

53055

Other (OTH)

AF:

0.00

AC:

AN:

1502

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000149

AC:

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.55

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.17

(source)

DANN

Benign

0.66

DEOGEN2

Benign

0.0026

FATHMM_MKL

Benign

0.038

LIST_S2

Benign

0.31

M_CAP

Benign

0.0024

MetaRNN

Benign

0.070

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.51

PhyloP100

-0.65

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.23

REVEL

Benign

0.0060

Sift

Benign

0.23

Sift4G

Benign

1.0

Polyphen

0.0030

Vest4

0.088

MVP

0.34

MPC

0.27

ClinPred

0.033

GERP RS

-2.6

Varity_R

0.037

gMVP

0.15

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over