NM_004538.6:c.1114G>T

Variant names:

• chrX-93672191-C-A
• rs758033690
• NM_004538.6:c.1114G>T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_004538.6(NAP1L3):​c.1114G>T​(p.Val372Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000546 in 1,098,224 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 3 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. V372M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., 0 hem., cov: 22)
  • Exomes 𝑓: 0.0000055 (0 hom. 3 hem.)
  • Failed GnomAD Quality Control
• Consequence: NAP1L3 NM_004538.6 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.189
• Publications: 0 publications found

Genes affected

NAP1L3 (HGNC:7639): (nucleosome assembly protein 1 like 3) This gene is intronless and encodes a member of the nucleosome assembly protein (NAP) family. This gene is linked closely to a region of genes responsible for several X-linked cognitive disability syndromes. [provided by RefSeq, Dec 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19779253).
• BS2: High Hemizygotes in GnomAdExome4 at 3 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004538.6. 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
	NAP1L3	NM_004538.6	MANE Select	c.1114G>T	p.Val372Leu	missense	Exon 1 of 1	NP_004529.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NAP1L3	ENST00000373079.4	TSL:6 MANE Select	c.1114G>T	p.Val372Leu	missense	Exon 1 of 1	ENSP00000362171.3	Q99457
	NAP1L3	ENST00000475430.2	TSL:2	c.1093G>T	p.Val365Leu	missense	Exon 2 of 2	ENSP00000476891.1	V9GYL6

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 111519 Hom.: 0 Cov.: 22

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

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: 0.00

GnomAD4 exome AF: 0.00000546 AC: 6 AN: 1098224 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 3 AN XY: 363580

African (AFR) AF: 0.00 AC: 0 AN: 26402

American (AMR) AF: 0.00 AC: 0 AN: 35206

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19382

East Asian (EAS) AF: 0.00 AC: 0 AN: 30205

South Asian (SAS) AF: 0.0000739 AC: 4 AN: 54145

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40533

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4137

European-Non Finnish (NFE) AF: 0.00000119 AC: 1 AN: 842117

Other (OTH) AF: 0.0000217 AC: 1 AN: 46097

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 111519 Hom.: 0 Cov.: 22 AF XY: 0.00 AC XY: 0 AN XY: 33699

African (AFR) AF: 0.00 AC: 0 AN: 30661

American (AMR) AF: 0.00 AC: 0 AN: 10481

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2635

East Asian (EAS) AF: 0.00 AC: 0 AN: 3543

South Asian (SAS) AF: 0.00 AC: 0 AN: 2648

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6004

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 237

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 53118

Other (OTH) AF: 0.00 AC: 0 AN: 1510

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	8.6
DANN	Benign	0.71
DEOGEN2	Benign	0.042	T
FATHMM_MKL	Benign	0.59	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.0027	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		0.19
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.12
Sift	Benign	0.34	T
Sift4G	Benign	0.44	T
Polyphen		0.44	B
Vest4		0.077
MutPred		0.71		Loss of methylation at K375 (P = 0.0831)
MVP		0.40
MPC		0.22
ClinPred		0.18	T
GERP RS		-2.8
Varity_R		0.093
gMVP		0.60
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs758033690; hg19: chrX-92927190;