Variant chr12-76067448-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 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

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 made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAP1L1	NM_004537.7 linkuse as main transcript	c.129G>A	p.Met43Ile	missense_variant	4/15	ENST00000618691.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAP1L1	ENST00000618691.5 linkuse as main transcript	c.129G>A	p.Met43Ile	missense_variant	4/15	1	NM_004537.7	P1	P55209-1

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

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2023

The c.129G>A (p.M43I) alteration is located in exon 4 (coding exon 3) of the NAP1L1 gene. This alteration results from a G to A substitution at nucleotide position 129, causing the methionine (M) at amino acid position 43 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.14

BayesDel_noAF

Uncertain

-0.040

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;T;T;T;.;.;T;.;T;T;T;T;T;.;.;T;T

Eigen

Uncertain

0.55

Eigen_PC

Uncertain

0.57

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

.;.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

M_CAP

Benign

0.021

MetaRNN

Uncertain

0.62

D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

MetaSVM

Benign

-0.81

MutationAssessor

Uncertain

2.7

M;M;.;M;.;.;.;M;.;.;.;.;.;.;.;.;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Benign

-2.1

.;N;N;N;N;N;N;N;N;N;N;N;N;D;D;D;D

REVEL

Benign

0.29

Sift

Uncertain

0.0090

.;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D;D

Sift4G

Uncertain

0.041

D;D;D;D;D;D;D;D;D;D;.;T;.;.;.;.;.

Polyphen

0.79

P;P;.;P;.;P;P;.;P;.;.;.;.;.;.;.;.

Vest4

0.61

MutPred

0.38

Loss of disorder (P = 0.061);Loss of disorder (P = 0.061);.;Loss of disorder (P = 0.061);.;.;Loss of disorder (P = 0.061);Loss of disorder (P = 0.061);Loss of disorder (P = 0.061);.;Loss of disorder (P = 0.061);Loss of disorder (P = 0.061);.;Loss of disorder (P = 0.061);Loss of disorder (P = 0.061);.;Loss of disorder (P = 0.061);

MVP

0.59

MPC

0.56

ClinPred

0.91

GERP RS

4.8

Varity_R

0.50

gMVP

0.33

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over