dbSNP rs752080473: NAP1L4:p.Met202Leu (chr11-2964682-T-A) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_005969.4(NAP1L4):c.604A>T(p.Met202Leu) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,136 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M202V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NAP1L4
NM_005969.4 missense, splice_region

Scores

Splicing: ADA: 0.7620

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 7.57

Variant links:

Genes affected

NAP1L4 (HGNC:7640): (nucleosome assembly protein 1 like 4) This gene encodes a member of the nucleosome assembly protein (NAP) family which can interact with both core and linker histones. It can shuttle between the cytoplasm and nucleus, suggesting a role as a histone chaperone. This gene is one of several located near the imprinted gene domain of 11p15.5, an important tumor-suppressor gene region. Alterations in this region have been associated with the Beckwith-Wiedemann syndrome, Wilms tumor, rhabdomyosarcoma, adrenocortical carcinoma, and lung, ovarian, and breast cancer. [provided by RefSeq, Jul 2008]

NAP1L4 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.34239337).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAP1L4	NM_005969.4 link	c.604A>T	p.Met202Leu	missense_variant, splice_region_variant	Exon 8 of 16	ENST00000380542.9	NP_005960.1	Q99733-1A0A024RCC9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAP1L4	ENST00000380542.9 link	c.604A>T	p.Met202Leu	missense_variant, splice_region_variant	Exon 8 of 16	1	NM_005969.4	ENSP00000369915.4		Q99733-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461136

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726914

show subpopulations

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:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.54

BayesDel_addAF

Uncertain

0.021

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.026

.;T;.;T;T

Eigen

Benign

0.021

Eigen_PC

Benign

0.14

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.67

.;.;.;T;.

M_CAP

Benign

0.0064

MetaRNN

Benign

0.34

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

L;L;L;.;.

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-2.3

.;N;N;N;N

REVEL

Benign

0.20

Sift

Benign

0.33

.;T;T;T;T

Sift4G

Benign

0.39

T;T;T;T;.

Polyphen

0.0040

.;B;.;.;.

Vest4

0.62

MutPred

0.46

Loss of sheet (P = 0.1501);Loss of sheet (P = 0.1501);Loss of sheet (P = 0.1501);.;.;

MVP

0.48

MPC

0.32

ClinPred

0.91

GERP RS

4.3

Varity_R

0.35

gMVP

0.29

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.76

dbscSNV1_RF

Benign

0.42

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

Other links and lift over