Variant 17-81629785-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_017921.4(NPLOC4):c.36G>A(p.Pro12Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.496 in 1,611,098 control chromosomes in the GnomAD database, including 207,066 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.57 ( 26334 hom., cov: 32)

Exomes 𝑓: 0.49 ( 180732 hom. )

Consequence

NPLOC4
NM_017921.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.29

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:

NPLOC4 (HGNC:):

NPLOC4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP7

Synonymous conserved (PhyloP=-3.29 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.752 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NPLOC4	NM_017921.4 linkuse as main transcript	c.36G>A	p.Pro12Pro	synonymous_variant	2/17	ENST00000331134.11	NP_060391.2	Q8TAT6-1A0A024R8R4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NPLOC4	ENST00000331134.11 linkuse as main transcript	c.36G>A	p.Pro12Pro	synonymous_variant	2/17	1	NM_017921.4	ENSP00000331487.5		Q8TAT6-1

Frequencies

GnomAD3 genomes

AF:

0.568

AC:

86350

AN:

151916

Hom.:

26276

Cov.:

show subpopulations

Gnomad AFR

AF:

0.755

Gnomad AMI

AF:

0.426

Gnomad AMR

AF:

0.624

Gnomad ASJ

AF:

0.518

Gnomad EAS

AF:

0.772

Gnomad SAS

AF:

0.645

Gnomad FIN

AF:

0.427

Gnomad MID

AF:

0.573

Gnomad NFE

AF:

0.448

Gnomad OTH

AF:

0.556

GnomAD3 exomes

AF:

0.557

AC:

138841

AN:

249138

Hom.:

41425

AF XY:

0.547

AC XY:

73873

AN XY:

135146

show subpopulations

Gnomad AFR exome

AF:

0.765

Gnomad AMR exome

AF:

0.734

Gnomad ASJ exome

AF:

0.511

Gnomad EAS exome

AF:

0.774

Gnomad SAS exome

AF:

0.629

Gnomad FIN exome

AF:

0.428

Gnomad NFE exome

AF:

0.452

Gnomad OTH exome

AF:

0.515

GnomAD4 exome

AF:

0.488

AC:

712096

AN:

1459064

Hom.:

180732

Cov.:

AF XY:

0.490

AC XY:

355711

AN XY:

725958

show subpopulations

Gnomad4 AFR exome

AF:

0.766

Gnomad4 AMR exome

AF:

0.723

Gnomad4 ASJ exome

AF:

0.513

Gnomad4 EAS exome

AF:

0.744

Gnomad4 SAS exome

AF:

0.619

Gnomad4 FIN exome

AF:

0.436

Gnomad4 NFE exome

AF:

0.451

Gnomad4 OTH exome

AF:

0.525

GnomAD4 genome

AF:

0.569

AC:

86463

AN:

152034

Hom.:

26334

Cov.:

AF XY:

0.569

AC XY:

42305

AN XY:

74286

show subpopulations

Gnomad4 AFR

AF:

0.755

Gnomad4 AMR

AF:

0.624

Gnomad4 ASJ

AF:

0.518

Gnomad4 EAS

AF:

0.772

Gnomad4 SAS

AF:

0.644

Gnomad4 FIN

AF:

0.427

Gnomad4 NFE

AF:

0.448

Gnomad4 OTH

AF:

0.562

Alfa

AF:

0.474

Hom.:

43175

Bravo

AF:

0.595

Asia WGS

AF:

0.741

AC:

2577

AN:

3478

EpiCase

AF:

0.447

EpiControl

AF:

0.451

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

2.4

DANN

Benign

0.72

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.7

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over