Variant chr17-81559406-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The ENST00000573519.5(NPLOC4):c.341C>T(p.Ala114Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00198 in 1,609,266 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0014 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0020 ( 3 hom. )

Consequence

NPLOC4
ENST00000573519.5 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -3.89

Variant links:

Genes affected

NPLOC4 (HGNC:18261): (NPL4 homolog, ubiquitin recognition factor) Predicted to enable ATPase binding activity; ubiquitin binding activity; and ubiquitin protein ligase binding activity. Predicted to contribute to K48-linked polyubiquitin modification-dependent protein binding activity and K63-linked polyubiquitin modification-dependent protein binding activity. Involved in negative regulation of RIG-I signaling pathway; negative regulation of type I interferon production; and proteolysis involved in cellular protein catabolic process. Located in nucleus. Part of UFD1-NPL4 complex and VCP-NPL4-UFD1 AAA ATPase complex. [provided by Alliance of Genome Resources, Apr 2022]

NPLOC4 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0069874823).

BP6

Variant 17-81559406-G-A is Benign according to our data. Variant chr17-81559406-G-A is described in ClinVar as [Benign]. Clinvar id is 788372.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPLOC4	NM_017921.4 linkuse as main transcript	c.1680C>T	p.Gly560=	synonymous_variant	17/17	ENST00000331134.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NPLOC4	ENST00000331134.11 linkuse as main transcript	c.1680C>T	p.Gly560=	synonymous_variant	17/17	1	NM_017921.4	P1	Q8TAT6-1

Frequencies

GnomAD3 genomes

AF:

0.00144

AC:

219

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000796

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00367

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00172

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00163

AC:

385

AN:

236128

Hom.:

AF XY:

0.00165

AC XY:

212

AN XY:

128674

show subpopulations

Gnomad AFR exome

AF:

0.000683

Gnomad AMR exome

AF:

0.00204

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000374

Gnomad FIN exome

AF:

0.00257

Gnomad NFE exome

AF:

0.00221

Gnomad OTH exome

AF:

0.00191

GnomAD4 exome

AF:

0.00203

AC:

2963

AN:

1456940

Hom.:

Cov.:

AF XY:

0.00194

AC XY:

1407

AN XY:

724368

show subpopulations

Gnomad4 AFR exome

AF:

0.000808

Gnomad4 AMR exome

AF:

0.00205

Gnomad4 ASJ exome

AF:

0.0000769

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000234

Gnomad4 FIN exome

AF:

0.00290

Gnomad4 NFE exome

AF:

0.00231

Gnomad4 OTH exome

AF:

0.00181

GnomAD4 genome

AF:

0.00144

AC:

219

AN:

152326

Hom.:

Cov.:

AF XY:

0.00141

AC XY:

105

AN XY:

74496

show subpopulations

Gnomad4 AFR

AF:

0.000794

Gnomad4 AMR

AF:

0.00176

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00367

Gnomad4 NFE

AF:

0.00172

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00142

Hom.:

Bravo

AF:

0.00133

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000244

AC:

ESP6500EA

AF:

0.00144

AC:

ExAC

AF:

0.00157

AC:

190

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Feb 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.63

BayesDel_noAF

Benign

-0.68

CADD

Benign

1.8

DANN

Benign

0.89

DEOGEN2

Benign

0.019

.;.;T

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.40

.;T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.0070

T;T;T

MutationTaster

Benign

1.0

D;N;N

Sift4G

Benign

0.10

.;.;T

Vest4

0.054

MVP

0.61

GERP RS

-9.7

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over