chr11-2955763-G-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

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_005969.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAP1L4	NM_005969.4	MANE Select	c.896C>T	p.Ser299Phe	missense	Exon 11 of 16	NP_005960.1	Q99733-1
	NAP1L4	NM_001369380.1		c.896C>T	p.Ser299Phe	missense	Exon 11 of 15	NP_001356309.1	Q99733-2
	NAP1L4	NM_001369381.1		c.896C>T	p.Ser299Phe	missense	Exon 12 of 16	NP_001356310.1	Q99733-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAP1L4	ENST00000380542.9	TSL:1 MANE Select	c.896C>T	p.Ser299Phe	missense	Exon 11 of 16	ENSP00000369915.4	Q99733-1
	NAP1L4	ENST00000955342.1		c.896C>T	p.Ser299Phe	missense	Exon 11 of 17	ENSP00000625401.1
	NAP1L4	ENST00000448187.6	TSL:5	c.932C>T	p.Ser311Phe	missense	Exon 11 of 15	ENSP00000387783.2	C9JZI7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000546

EpiControl AF: 0.00

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		5.1
PrimateAI	Uncertain	0.65	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.17
Sift	Uncertain	0.027	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.043	B
Vest4		0.63
MutPred		0.54		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
Mutation Taster		=76/24	polymorphism

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

Other links and lift over

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