dbSNP rs779412852: NAP1L1:p.Ala321Val (chr12-76050628-G-A) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004537.7(NAP1L1):c.962C>T(p.Ala321Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000931 in 1,610,970 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000096 ( 0 hom. )

Consequence

NAP1L1
NM_004537.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 10.0

Publications

1 publications found

Variant links:

Genes affected

NAP1L1 (HGNC:7637): (nucleosome assembly protein 1 like 1) This gene encodes a member of the nucleosome assembly protein (NAP) family. This protein participates in DNA replication and may play a role in modulating chromatin formation and contribute to the regulation of cell proliferation. Alternative splicing results in multiple transcript variants encoding different isoforms; however, not all have been fully described. [provided by RefSeq, Apr 2015]

NAP1L1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004537.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAP1L1	NM_004537.7	MANE Select	c.962C>T	p.Ala321Val	missense	Exon 12 of 15	NP_004528.1	P55209-1
NAP1L1	NM_001330231.2		c.962C>T	p.Ala321Val	missense	Exon 12 of 16	NP_001317160.1	P55209-1
NAP1L1	NM_139207.5		c.962C>T	p.Ala321Val	missense	Exon 12 of 16	NP_631946.1	P55209-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
NAP1L1	ENST00000618691.5	TSL:1 MANE Select	c.962C>T	p.Ala321Val	missense	Exon 12 of 15	ENSP00000477538.1	P55209-1
NAP1L1	ENST00000393263.7	TSL:1	c.962C>T	p.Ala321Val	missense	Exon 12 of 16	ENSP00000376947.3	P55209-1
NAP1L1	ENST00000547993.5	TSL:1	n.2257C>T		non_coding_transcript_exon	Exon 6 of 8

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152102

Hom.:

Cov.:

show subpopulations

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000404

AC:

AN:

247570

AF XY:

0.00

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:

0.00000888

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000960

AC:

AN:

1458868

Hom.:

Cov.:

AF XY:

0.00000965

AC XY:

AN XY:

725686

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33292

American (AMR)

AF:

0.00

AC:

AN:

43778

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26026

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.00

AC:

AN:

85514

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5748

European-Non Finnish (NFE)

AF:

0.0000126

AC:

AN:

1111256

Other (OTH)

AF:

0.00

AC:

AN:

60248

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

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:

0.00000657

AC:

AN:

152102

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41414

American (AMR)

AF:

0.00

AC:

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10596

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68012

Other (OTH)

AF:

0.00

AC:

AN:

2088

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:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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

Pathogenic

0.93

BayesDel_addAF

Uncertain

0.075

BayesDel_noAF

Benign

-0.13

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.22

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.97

M_CAP

Benign

0.038

MetaRNN

Uncertain

0.60

MetaSVM

Benign

-0.64

MutationAssessor

Pathogenic

3.1

PhyloP100

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-2.2

REVEL

Benign

0.28

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.043

Polyphen

0.43

Vest4

0.72

MutPred

0.54

Loss of helix (P = 0.028)

MVP

0.43

MPC

1.0

ClinPred

0.91

GERP RS

5.5

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

Varity_R

0.40

gMVP

0.33

Mutation Taster

=16/84

disease causing

(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