NM_004537.7:c.111G>T

Variant names:

• chr12-76067466-C-A
• NM_004537.7:c.111G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004537.7(NAP1L1):​c.111G>T​(p.Gln37His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NAP1L1 NM_004537.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.60
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27562398).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004537.7. 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
	NAP1L1	NM_004537.7	MANE Select	c.111G>T	p.Gln37His	missense	Exon 4 of 15	NP_004528.1	P55209-1
	NAP1L1	NM_001330231.2		c.111G>T	p.Gln37His	missense	Exon 4 of 16	NP_001317160.1	P55209-1
	NAP1L1	NM_139207.5		c.111G>T	p.Gln37His	missense	Exon 4 of 16	NP_631946.1	P55209-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAP1L1	ENST00000618691.5	TSL:1 MANE Select	c.111G>T	p.Gln37His	missense	Exon 4 of 15	ENSP00000477538.1	P55209-1
	NAP1L1	ENST00000393263.7	TSL:1	c.111G>T	p.Gln37His	missense	Exon 4 of 16	ENSP00000376947.3	P55209-1
	NAP1L1	ENST00000880560.1		c.111G>T	p.Gln37His	missense	Exon 4 of 15	ENSP00000550619.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1443818 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 717638

African (AFR) AF: 0.00 AC: 0 AN: 33086

American (AMR) AF: 0.00 AC: 0 AN: 43290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25632

East Asian (EAS) AF: 0.00 AC: 0 AN: 39470

South Asian (SAS) AF: 0.00 AC: 0 AN: 84494

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50440

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5688

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1102158

Other (OTH) AF: 0.00 AC: 0 AN: 59560

GnomAD4 genome Cov.: 32

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	0.28
BayesDel_addAF	Benign	-0.036	T
BayesDel_noAF	Benign	-0.29
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.083
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.28	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		2.6
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.12
Sift	Benign	0.16	T
Sift4G	Benign	0.096	T
Polyphen		0.057	B
Vest4		0.57
MutPred		0.32		Loss of helix (P = 0.0017)
MVP		0.61
MPC		0.54
ClinPred		0.55	D
GERP RS		1.8
PromoterAI		0.026	Neutral
Varity_R		0.12
gMVP		0.30
Mutation Taster		=46/54	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: chr12-76461246;