NM_004537.7:c.1105G>A

Variant names:

• chr12-76049235-C-T
• rs896846690
• NM_004537.7:c.1105G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004537.7(NAP1L1):​c.1105G>A​(p.Gly369Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000136 in 1,613,382 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000048 (0 hom.)
• Consequence: NAP1L1 NM_004537.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.47
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.17068616).

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.1105G>A	p.Gly369Arg	missense	Exon 14 of 15	NP_004528.1	P55209-1
	NAP1L1	NM_001330231.2		c.1105G>A	p.Gly369Arg	missense	Exon 14 of 16	NP_001317160.1	P55209-1
	NAP1L1	NM_139207.5		c.1105G>A	p.Gly369Arg	missense	Exon 14 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.1105G>A	p.Gly369Arg	missense	Exon 14 of 15	ENSP00000477538.1	P55209-1
	NAP1L1	ENST00000393263.7	TSL:1	c.1105G>A	p.Gly369Arg	missense	Exon 14 of 16	ENSP00000376947.3	P55209-1
	NAP1L1	ENST00000880560.1		c.1105G>A	p.Gly369Arg	missense	Exon 14 of 15	ENSP00000550619.1

Frequencies

GnomAD3 genomes AF: 0.0000987 AC: 15 AN: 152044 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000266

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000959

GnomAD2 exomes AF: 0.00000797 AC: 2 AN: 250808 AF XY: 0.00000738

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000479 AC: 7 AN: 1461338 Hom.: 0 Cov.: 31 AF XY: 0.00000275 AC XY: 2 AN XY: 726980

African (AFR) AF: 0.000149 AC: 5 AN: 33450

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39648

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53268

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111770

Other (OTH) AF: 0.0000331 AC: 2 AN: 60366

GnomAD4 genome AF: 0.0000987 AC: 15 AN: 152044 Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7 AN XY: 74270

African (AFR) AF: 0.000266 AC: 11 AN: 41418

American (AMR) AF: 0.000131 AC: 2 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5194

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67954

Other (OTH) AF: 0.000959 AC: 2 AN: 2086

Alfa AF: 0.0000775 Hom.: 0

Bravo AF: 0.000121

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	Pathogenic	0.76
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.39
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.17	T
Eigen	Benign	0.15
Eigen_PC	Uncertain	0.34
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.0075	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		5.5
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.042
Sift	Benign	0.045	D
Sift4G	Benign	0.29	T
Polyphen		0.077	B
Vest4		0.22
MutPred		0.27		Gain of solvent accessibility (P = 0.0097)
MVP		0.12
MPC		0.61
ClinPred		0.22	T
GERP RS		6.0
Varity_R		0.18
gMVP		0.061
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs896846690; hg19: chr12-76443015;