Variant chr17-81559353-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_017921.4(NPLOC4):c.1733C>T(p.Thr578Met) variant causes a missense change. The variant allele was found at a frequency of 0.00119 in 1,607,754 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0054 ( 9 hom., cov: 33)

Exomes 𝑓: 0.00076 ( 5 hom. )

Consequence

NPLOC4
NM_017921.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.95

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003497541).

BP6

Variant 17-81559353-G-A is Benign according to our data. Variant chr17-81559353-G-A is described in ClinVar as [Benign]. Clinvar id is 777257.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00536 (816/152354) while in subpopulation AFR AF= 0.0184 (767/41588). AF 95% confidence interval is 0.0174. There are 9 homozygotes in gnomad4. There are 382 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NPLOC4	NM_017921.4 linkuse as main transcript	c.1733C>T	p.Thr578Met	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.1733C>T	p.Thr578Met	missense_variant	17/17	1	NM_017921.4	P1	Q8TAT6-1

Frequencies

GnomAD3 genomes

AF:

0.00532

AC:

810

AN:

152236

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00163

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.00335

GnomAD3 exomes

AF:

0.00154

AC:

360

AN:

233520

Hom.:

AF XY:

0.00118

AC XY:

150

AN XY:

127468

show subpopulations

Gnomad AFR exome

AF:

0.0207

Gnomad AMR exome

AF:

0.000848

Gnomad ASJ exome

AF:

0.000103

Gnomad EAS exome

AF:

0.000230

Gnomad SAS exome

AF:

0.0000686

Gnomad FIN exome

AF:

0.0000515

Gnomad NFE exome

AF:

0.000285

Gnomad OTH exome

AF:

0.000702

GnomAD4 exome

AF:

0.000758

AC:

1103

AN:

1455400

Hom.:

Cov.:

AF XY:

0.000697

AC XY:

504

AN XY:

723434

show subpopulations

Gnomad4 AFR exome

AF:

0.0220

Gnomad4 AMR exome

AF:

0.00101

Gnomad4 ASJ exome

AF:

0.0000385

Gnomad4 EAS exome

AF:

0.0000760

Gnomad4 SAS exome

AF:

0.000118

Gnomad4 FIN exome

AF:

0.0000572

Gnomad4 NFE exome

AF:

0.000167

Gnomad4 OTH exome

AF:

0.00180

GnomAD4 genome

AF:

0.00536

AC:

816

AN:

152354

Hom.:

Cov.:

AF XY:

0.00513

AC XY:

382

AN XY:

74508

show subpopulations

Gnomad4 AFR

AF:

0.0184

Gnomad4 AMR

AF:

0.00163

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000235

Gnomad4 OTH

AF:

0.00332

Alfa

AF:

0.00197

Hom.:

Bravo

AF:

0.00657

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.0201

AC:

ESP6500EA

AF:

0.000119

AC:

ExAC

AF:

0.00192

AC:

232

Asia WGS

AF:

0.00375

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.68

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.84

DEOGEN2

Benign

0.0070

.;.;T

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.70

FATHMM_MKL

Benign

0.67

LIST_S2

Benign

0.63

.;T;T

MetaRNN

Benign

0.0035

T;T;T

MutationTaster

Benign

1.0

N;N;N

Sift4G

Uncertain

0.028

.;.;D

Vest4

0.18

MVP

0.35

ClinPred

0.010

GERP RS

1.6

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

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