Variant 11-2969836-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005969.4(NAP1L4):c.501C>G(p.Phe167Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,368 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NAP1L4
NM_005969.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.535

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NAP1L4	NM_005969.4 linkuse as main transcript	c.501C>G	p.Phe167Leu	missense_variant	7/16	ENST00000380542.9	NP_005960.1	Q99733-1A0A024RCC9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NAP1L4	ENST00000380542.9 linkuse as main transcript	c.501C>G	p.Phe167Leu	missense_variant	7/16	1	NM_005969.4	ENSP00000369915.4		Q99733-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461368

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

726938

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:

8.99e-7

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

Jun 06, 2023

The c.501C>G (p.F167L) alteration is located in exon 7 (coding exon 6) of the NAP1L4 gene. This alteration results from a C to G substitution at nucleotide position 501, causing the phenylalanine (F) at amino acid position 167 to be replaced by a leucine (L). 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

0.90

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.13

.;T;.;T;T;T

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.3

FATHMM_MKL

Uncertain

0.94

M_CAP

Benign

0.017

MetaRNN

Uncertain

0.53

D;D;D;D;D;D

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.3

L;L;L;.;.;.

PrimateAI

Pathogenic

0.83

PROVEAN

Pathogenic

-4.4

.;D;D;D;D;D

REVEL

Benign

0.28

Sift

Benign

0.38

.;T;T;T;T;T

Sift4G

Benign

0.58

T;T;T;.;T;T

Polyphen

0.11

.;B;.;.;.;.

Vest4

0.88

MutPred

0.61

Gain of helix (P = 0.132);Gain of helix (P = 0.132);Gain of helix (P = 0.132);.;.;Gain of helix (P = 0.132);

MVP

0.61

MPC

0.89

ClinPred

0.97

GERP RS

-5.4

RBP_binding_hub_radar

0.92

RBP_regulation_power_radar

3.7

Varity_R

0.36

gMVP

0.56

Splicing

Name

Calibrated prediction

Score

Prediction

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

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