Genetic Variant NAP1L4:p.Asn294Ser (chr11-2958410-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_005969.4(NAP1L4):c.881A>G(p.Asn294Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,614,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000053 ( 0 hom. )

Consequence

NAP1L4
NM_005969.4 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.387

Publications

0 publications found

Variant links:

Genes affected

NAP1L4 (HGNC:7640): (nucleosome assembly protein 1 like 4) This gene encodes a member of the nucleosome assembly protein (NAP) family which can interact with both core and linker histones. It can shuttle between the cytoplasm and nucleus, suggesting a role as a histone chaperone. This gene is one of several located near the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. [provided by RefSeq, Jul 2008]

NAP1L4 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048110366).

BP6

Variant 11-2958410-T-C is Benign according to our data. Variant chr11-2958410-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2339367.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 10 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005969.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAP1L4	NM_005969.4	MANE Select	c.881A>G	p.Asn294Ser	missense	Exon 10 of 16	NP_005960.1	Q99733-1
NAP1L4	NM_001369380.1		c.881A>G	p.Asn294Ser	missense	Exon 10 of 15	NP_001356309.1	Q99733-2
NAP1L4	NM_001369381.1		c.881A>G	p.Asn294Ser	missense	Exon 11 of 16	NP_001356310.1	Q99733-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAP1L4	ENST00000380542.9	TSL:1 MANE Select	c.881A>G	p.Asn294Ser	missense	Exon 10 of 16	ENSP00000369915.4	Q99733-1
NAP1L4	ENST00000955342.1		c.881A>G	p.Asn294Ser	missense	Exon 10 of 17	ENSP00000625401.1
NAP1L4	ENST00000448187.6	TSL:5	c.917A>G	p.Asn306Ser	missense	Exon 10 of 15	ENSP00000387783.2	C9JZI7

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

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:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000722

AC:

AN:

249326

AF XY:

0.0000739

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:

0.000464

Gnomad NFE exome

AF:

0.0000530

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

AF:

0.0000527

AC:

AN:

1461736

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

727166

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33468

American (AMR)

AF:

0.00

AC:

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26134

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000580

AC:

AN:

86214

European-Finnish (FIN)

AF:

0.000599

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.0000324

AC:

AN:

1111958

Other (OTH)

AF:

0.0000331

AC:

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000656

AC:

AN:

152338

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41572

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.000377

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68040

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

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:

0.0000564

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000910

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.041

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.9

(source)

DANN

Benign

0.19

DEOGEN2

Benign

0.0070

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.047

M_CAP

Benign

0.0059

MetaRNN

Benign

0.048

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.33

PhyloP100

0.39

PrimateAI

Benign

0.33

PROVEAN

Benign

-0.50

REVEL

Benign

0.064

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0020

Vest4

0.11

MutPred

0.42

Gain of phosphorylation at N294 (P = 0.0579)

MVP

0.33

MPC

0.19

ClinPred

0.012

GERP RS

-1.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.020

gMVP

0.065

Mutation Taster

=95/5

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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