Genetic Variant NAP1L1:p.Asp353Tyr (chr12-76050533-C-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.1057G>T(p.Asp353Tyr) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000482 in 1,452,374 control chromosomes in the GnomAD database, with no homozygous occurrence. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

NAP1L1
NM_004537.7 missense, splice_region

Scores

Splicing: ADA: 0.1467

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.88

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.1057G>T	p.Asp353Tyr	missense splice_region	Exon 12 of 15	NP_004528.1	P55209-1
NAP1L1	NM_001330231.2		c.1057G>T	p.Asp353Tyr	missense splice_region	Exon 12 of 16	NP_001317160.1	P55209-1
NAP1L1	NM_139207.5		c.1057G>T	p.Asp353Tyr	missense splice_region	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.1057G>T	p.Asp353Tyr	missense splice_region	Exon 12 of 15	ENSP00000477538.1	P55209-1
NAP1L1	ENST00000393263.7	TSL:1	c.1057G>T	p.Asp353Tyr	missense splice_region	Exon 12 of 16	ENSP00000376947.3	P55209-1
NAP1L1	ENST00000547993.5	TSL:1	n.2352G>T		splice_region non_coding_transcript_exon	Exon 6 of 8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000834

AC:

AN:

239776

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:

0.0000182

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000482

AC:

AN:

1452374

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

722334

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32946

American (AMR)

AF:

0.00

AC:

AN:

42312

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25704

East Asian (EAS)

AF:

0.00

AC:

AN:

39566

South Asian (SAS)

AF:

0.00

AC:

AN:

84188

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53242

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5050

European-Non Finnish (NFE)

AF:

0.00000631

AC:

AN:

1109430

Other (OTH)

AF:

0.00

AC:

AN:

59936

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

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

Cov.:

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.00000378

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000165

AC:

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

0.64

BayesDel_addAF

Uncertain

0.067

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.35

Eigen

Uncertain

0.60

Eigen_PC

Uncertain

0.65

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.88

M_CAP

Benign

0.028

MetaRNN

Uncertain

0.51

MetaSVM

Benign

-0.74

MutationAssessor

Uncertain

2.4

PhyloP100

7.9

PrimateAI

Pathogenic

0.88

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.21

Sift

Benign

0.32

Sift4G

Benign

0.11

Polyphen

0.98

Vest4

0.72

MVP

0.42

MPC

0.62

ClinPred

0.75

GERP RS

5.7

Varity_R

0.24

gMVP

0.44

Mutation Taster

=9/91

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.15

dbscSNV1_RF

Benign

0.34

SpliceAI score (max)

0.0

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over