chr12-76056118-T-C

Variant names:

• chr12-76056118-T-C
• rs1211567960
• NM_004537.7:c.473A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004537.7(NAP1L1):​c.473A>G​(p.Asp158Gly) 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 benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: NAP1L1 NM_004537.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.01

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32751548).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NAP1L1	NM_004537.7	c.473A>G	p.Asp158Gly	missense_variant	Exon 7 of 15	ENST00000618691.5	NP_004528.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NAP1L1	ENST00000618691.5	c.473A>G	p.Asp158Gly	missense_variant	Exon 7 of 15	1	NM_004537.7	ENSP00000477538.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.0085	T
BayesDel_noAF	Benign	-0.25
CADD	Pathogenic	28
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T;T;T;T;.;T;.;T;.;T;T;T;T;T;.;.
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.92	.;.;D;D;T;D;D;D;D;T;D;T;T;D;D;D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.33	T;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;L;.;L;.;.;.;.;L;.;.;.;.;.;.;.
PrimateAI	Uncertain	0.59	T
PROVEAN	Uncertain	-2.8	.;D;D;D;D;D;D;D;D;N;D;D;D;D;D;N
REVEL	Benign	0.20
Sift	Benign	0.095	.;T;T;T;T;T;T;T;T;T;T;T;T;T;T;T
Sift4G	Benign	0.14	T;T;T;T;T;T;T;T;T;T;T;.;T;.;.;.
Polyphen		0.0030	B;B;.;B;.;B;B;B;.;B;.;.;.;.;.;.
Vest4		0.44
MutPred		0.31		Gain of ubiquitination at K161 (P = 0.0743);Gain of ubiquitination at K161 (P = 0.0743);.;Gain of ubiquitination at K161 (P = 0.0743);.;.;.;Gain of ubiquitination at K161 (P = 0.0743);Gain of ubiquitination at K161 (P = 0.0743);.;.;.;Gain of ubiquitination at K161 (P = 0.0743);.;.;.;
MVP		0.62
MPC		0.67
ClinPred		0.86	D
GERP RS		6.0
Varity_R		0.33
gMVP		0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.17		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: rs1211567960; hg19: chr12-76449898;