12-76068915-G-A

Position:

• chr12-76068915-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004537.7(NAP1L1):​c.97C>T​(p.Leu33Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAP1L1 NM_004537.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.54

Genes affected

NAP1L1 (HGNC:7637): (nucleosome assembly protein 1 like 1) This gene encodes a member of the nucleosome assembly protein (NAP) family. This protein participates in DNA replication and may play a role in modulating chromatin formation and contribute to the regulation of cell proliferation. Alternative splicing results in multiple transcript variants encoding different isoforms; however, not all have been fully described. [provided by RefSeq, Apr 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1013).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NAP1L1	NM_004537.7	c.97C>T	p.Leu33Phe	missense_variant	3/15	ENST00000618691.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NAP1L1	ENST00000618691.5	c.97C>T	p.Leu33Phe	missense_variant	3/15	1	NM_004537.7	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 06, 2021

The c.97C>T (p.L33F) alteration is located in exon 3 (coding exon 2) of the NAP1L1 gene. This alteration results from a C to T substitution at nucleotide position 97, causing the leucine (L) at amino acid position 33 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	0.10
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	19
DANN	Benign	0.86
DEOGEN2	Benign	0.11	T;T;T;T;T;.;T;T;T;.;.;T
Eigen	Benign	-0.35
Eigen_PC	Benign	-0.14
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.81	.;.;T;T;T;T;T;T;T;T;T;T
M_CAP	Benign	0.0068	T
MetaRNN	Benign	0.10	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;N;.;N;.;N;.;.;.;.;.;.
MutationTaster	Benign	1.0	D;D;D;D;D;N;N;N;N;N
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-0.80	.;N;N;N;N;N;N;N;N;N;N;N
REVEL	Benign	0.035
Sift	Benign	0.74	.;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.67	T;T;T;T;T;T;T;.;T;.;.;.
Polyphen		0.0010	B;B;.;B;B;.;B;.;.;.;.;.
Vest4		0.13
MutPred		0.30		Gain of methylation at K32 (P = 0.0279);Gain of methylation at K32 (P = 0.0279);.;Gain of methylation at K32 (P = 0.0279);Gain of methylation at K32 (P = 0.0279);Gain of methylation at K32 (P = 0.0279);Gain of methylation at K32 (P = 0.0279);Gain of methylation at K32 (P = 0.0279);Gain of methylation at K32 (P = 0.0279);Gain of methylation at K32 (P = 0.0279);Gain of methylation at K32 (P = 0.0279);Gain of methylation at K32 (P = 0.0279);
MVP		0.24
MPC		0.56
ClinPred		0.51	D
GERP RS		4.3
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.050

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: chr12-76462695;