Genetic Variant NM_004537.7:c.1130A>G (chr12-76049210-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_004537.7(NAP1L1):c.1130A>G(p.Tyr377Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000527 in 1,613,486 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

NAP1L1
NM_004537.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.56

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15883246).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAP1L1	NM_004537.7 link	c.1130A>G	p.Tyr377Cys	missense_variant	Exon 14 of 15	ENST00000618691.5	NP_004528.1	P55209-1A0A024RBB7Q9H2B0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAP1L1	ENST00000618691.5 link	c.1130A>G	p.Tyr377Cys	missense_variant	Exon 14 of 15	1	NM_004537.7	ENSP00000477538.1		P55209-1

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000241

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000359

AC:

AN:

250842

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135606

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.000327

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1461330

Hom.:

Cov.:

AF XY:

0.0000481

AC XY:

AN XY:

726976

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000757

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000513

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152156

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000434

Hom.:

Bravo

AF:

0.000128

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1130A>G (p.Y377C) alteration is located in exon 14 (coding exon 13) of the NAP1L1 gene. This alteration results from a A to G substitution at nucleotide position 1130, causing the tyrosine (Y) at amino acid position 377 to be replaced by a cysteine (C). 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

Uncertain

0.47

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.23

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.33

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

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.52

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

M_CAP

Benign

0.013

MetaRNN

Benign

0.16

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

L;L;.;L;.;.;.;.

PrimateAI

Pathogenic

0.81

PROVEAN

Uncertain

-2.8

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

REVEL

Benign

0.11

Sift

Benign

0.065

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

Sift4G

Benign

0.17

T;T;T;T;T;T;T;T

Polyphen

0.94

P;P;.;P;.;B;.;P

Vest4

0.56

MVP

0.31

MPC

0.90

ClinPred

0.079

GERP RS

6.0

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.13

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over