rs930988016

Variant names:

• chr11-2969816-C-T
• rs930988016
• NM_005969.4:c.521G>A

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2 PP3

The NM_005969.4(NAP1L4):​c.521G>A​(p.Ser174Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 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: 7.49
• 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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.788

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.521G>A	p.Ser174Asn	missense	Exon 7 of 16	NP_005960.1	Q99733-1
	NAP1L4	NM_001369380.1		c.521G>A	p.Ser174Asn	missense	Exon 7 of 15	NP_001356309.1	Q99733-2
	NAP1L4	NM_001369381.1		c.521G>A	p.Ser174Asn	missense	Exon 8 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.521G>A	p.Ser174Asn	missense	Exon 7 of 16	ENSP00000369915.4	Q99733-1
	NAP1L4	ENST00000955342.1		c.521G>A	p.Ser174Asn	missense	Exon 7 of 17	ENSP00000625401.1
	NAP1L4	ENST00000448187.6	TSL:5	c.557G>A	p.Ser186Asn	missense	Exon 7 of 15	ENSP00000387783.2	C9JZI7

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

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	0.34
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	0.98
DEOGEN2	Benign	0.036	T
Eigen	Benign	0.077
Eigen_PC	Benign	0.0053
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.022	T
MetaRNN	Pathogenic	0.79	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		7.5
PrimateAI	Pathogenic	0.80	T
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.31
Sift	Benign	0.071	T
Sift4G	Benign	0.061	T
Polyphen		0.72	P
Vest4		0.80
MutPred		0.75		Gain of loop (P = 0.2045)
MVP		0.37
MPC		0.81
ClinPred		0.89	D
GERP RS		4.2
Varity_R		0.29
gMVP		0.52
Mutation Taster		=49/51	disease causing

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

dbSNP: rs930988016; hg19: chr11-2991046;