NM_004537.7:c.1130A>T

Variant names:

• chr12-76049210-T-A
• rs149910881
• NM_004537.7:c.1130A>T

Variant summary

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

The NM_004537.7(NAP1L1):​c.1130A>T​(p.Tyr377Phe) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: NAP1L1 NM_004537.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.56

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=0.1370646).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAP1L1	NM_004537.7	c.1130A>T	p.Tyr377Phe	missense_variant	Exon 14 of 15	ENST00000618691.5	NP_004528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAP1L1	ENST00000618691.5	c.1130A>T	p.Tyr377Phe	missense_variant	Exon 14 of 15	1	NM_004537.7	ENSP00000477538.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.096
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.11	T;T;T;T;.;T;T;.
Eigen	Benign	-0.20
Eigen_PC	Benign	0.080
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.50	.;.;T;T;T;T;T;T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.14	T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.88	L;L;.;L;.;.;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.73	.;N;N;N;N;N;N;N
REVEL	Benign	0.071
Sift	Benign	0.31	.;T;T;T;T;T;T;T
Sift4G	Benign	0.70	T;T;T;T;T;T;T;T
Polyphen		0.0	B;B;.;B;.;B;.;B
Vest4		0.35
MutPred		0.23		Loss of phosphorylation at Y377 (P = 0.0025);Loss of phosphorylation at Y377 (P = 0.0025);.;Loss of phosphorylation at Y377 (P = 0.0025);.;.;.;.;
MVP		0.43
MPC		0.45
ClinPred		0.41	T
GERP RS		6.0
Varity_R		0.082
gMVP		0.056

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

LitVar

Other links and lift over

dbSNP: rs149910881; hg19: chr12-76442990;