Variant chr17-81559396-G-C 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 NM_017921.4(NPLOC4):c.1690C>G(p.Pro564Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00332 in 1,610,498 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0025 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0034 ( 11 hom. )

Consequence

NPLOC4
NM_017921.4 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.89

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=0.0073135197).

BP6

Variant 17-81559396-G-C is Benign according to our data. Variant chr17-81559396-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 769931.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 11 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPLOC4	NM_017921.4 linkuse as main transcript	c.1690C>G	p.Pro564Ala	missense_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.1690C>G	p.Pro564Ala	missense_variant	17/17	1	NM_017921.4	P1	Q8TAT6-1

Frequencies

GnomAD3 genomes

AF:

0.00250

AC:

381

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00373

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00397

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00213

AC:

508

AN:

238272

Hom.:

AF XY:

0.00216

AC XY:

281

AN XY:

129908

show subpopulations

Gnomad AFR exome

AF:

0.000543

Gnomad AMR exome

AF:

0.00274

Gnomad ASJ exome

AF:

0.00347

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000337

Gnomad FIN exome

AF:

0.000150

Gnomad NFE exome

AF:

0.00322

Gnomad OTH exome

AF:

0.00275

GnomAD4 exome

AF:

0.00340

AC:

4964

AN:

1458178

Hom.:

Cov.:

AF XY:

0.00326

AC XY:

2364

AN XY:

725054

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.00267

Gnomad4 ASJ exome

AF:

0.00342

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000327

Gnomad4 FIN exome

AF:

0.000246

Gnomad4 NFE exome

AF:

0.00408

Gnomad4 OTH exome

AF:

0.00276

GnomAD4 genome

AF:

0.00250

AC:

381

AN:

152320

Hom.:

Cov.:

AF XY:

0.00238

AC XY:

177

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00372

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.00397

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00260

Hom.:

Bravo

AF:

0.00255

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.000486

AC:

ESP6500EA

AF:

0.00275

AC:

ExAC

AF:

0.00195

AC:

236

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Nov 19, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.052

Eigen

Benign

-0.17

Eigen_PC

Benign

0.0067

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.82

M_CAP

Benign

0.0050

MetaRNN

Benign

0.0073

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.7

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.9

REVEL

Benign

0.035

Sift

Benign

0.16

Sift4G

Benign

0.24

Polyphen

0.059

Vest4

0.077

MVP

0.40

MPC

0.014

ClinPred

0.0074

GERP RS

4.8

RBP_binding_hub_radar

1.1

RBP_regulation_power_radar

2.8

Varity_R

0.062

gMVP

0.20

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