Genetic Variant NAP1L1:p.Met43Ile (chr12-76067448-C-T) – 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.129G>A(p.Met43Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

NAP1L1
NM_004537.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.68

Publications

0 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:

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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.129G>A	p.Met43Ile	missense	Exon 4 of 15	NP_004528.1	P55209-1
NAP1L1	NM_001330231.2		c.129G>A	p.Met43Ile	missense	Exon 4 of 16	NP_001317160.1	P55209-1
NAP1L1	NM_139207.5		c.129G>A	p.Met43Ile	missense	Exon 4 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.129G>A	p.Met43Ile	missense	Exon 4 of 15	ENSP00000477538.1	P55209-1
NAP1L1	ENST00000393263.7	TSL:1	c.129G>A	p.Met43Ile	missense	Exon 4 of 16	ENSP00000376947.3	P55209-1
NAP1L1	ENST00000880560.1		c.129G>A	p.Met43Ile	missense	Exon 4 of 15	ENSP00000550619.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1455142

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

723900

African (AFR)

AF:

0.00

AC:

AN:

33416

American (AMR)

AF:

0.00

AC:

AN:

44676

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25958

East Asian (EAS)

AF:

0.00

AC:

AN:

39624

South Asian (SAS)

AF:

0.00

AC:

AN:

85818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5730

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108072

Other (OTH)

AF:

0.00

AC:

AN:

60080

GnomAD4 genome

Cov.:

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

0.95

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.62

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.7

PhyloP100

7.7

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-2.1

REVEL

Benign

0.29

Sift

Uncertain

0.0090

Sift4G

Uncertain

0.041

Polyphen

0.79

Vest4

0.61

MutPred

0.38

Loss of disorder (P = 0.061)

MVP

0.59

MPC

0.56

ClinPred

0.91

GERP RS

4.8

PromoterAI

-0.080

Neutral

(source)

Varity_R

0.50

gMVP

0.33

Mutation Taster

=8/92

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over