11-2955763-G-A

Variant names:

• chr11-2955763-G-A
• NM_005969.4:c.896C>T

Variant summary

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

The NM_005969.4(NAP1L4):​c.896C>T​(p.Ser299Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAP1L4 NM_005969.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.06

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]

ACMG classification

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 rank	MANE	Protein	UniProt
NAP1L4	NM_005969.4	c.896C>T	p.Ser299Phe	missense_variant	Exon 11 of 16	ENST00000380542.9	NP_005960.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAP1L4	ENST00000380542.9	c.896C>T	p.Ser299Phe	missense_variant	Exon 11 of 16	1	NM_005969.4	ENSP00000369915.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 17, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.896C>T (p.S299F) alteration is located in exon 11 (coding exon 10) of the NAP1L4 gene. This alteration results from a C to T substitution at nucleotide position 896, causing the serine (S) at amino acid position 299 to be replaced by a phenylalanine (F). 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	Benign	0.16
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	.;T;.
Eigen	Benign	0.0040
Eigen_PC	Benign	0.0075
FATHMM_MKL	Pathogenic	0.97	D
M_CAP	Benign	0.017	T
MetaRNN	Uncertain	0.64	D;D;D
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.4	M;M;M
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.5	.;D;D
REVEL	Benign	0.17
Sift	Uncertain	0.027	.;D;D
Sift4G	Uncertain	0.0040	D;D;D
Polyphen		0.043	.;B;.
Vest4		0.63
MutPred		0.54		Loss of glycosylation at S299 (P = 0.0094);Loss of glycosylation at S299 (P = 0.0094);Loss of glycosylation at S299 (P = 0.0094);
MVP		0.39
MPC		0.62
ClinPred		0.93	D
GERP RS		3.9
Varity_R		0.29
gMVP		0.25

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.

Other links and lift over

hg19: chr11-2976993; COSMIC: COSV65882413; COSMIC: COSV65882413;