17-81629785-C-G

Variant names:

• chr17-81629785-C-G
• rs9894429
• NM_017921.4:c.36G>C

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_017921.4(NPLOC4):​c.36G>C​(p.Pro12Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: NPLOC4 NM_017921.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.29
• Publications: 62 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP7: Synonymous conserved (PhyloP=-3.29 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017921.4. 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
	NPLOC4	NM_017921.4	MANE Select	c.36G>C	p.Pro12Pro	synonymous	Exon 2 of 17	NP_060391.2	Q8TAT6-1
	NPLOC4	NM_001437986.1		c.36G>C	p.Pro12Pro	synonymous	Exon 2 of 16	NP_001424915.1
	NPLOC4	NM_001369698.1		c.36G>C	p.Pro12Pro	synonymous	Exon 2 of 17	NP_001356627.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NPLOC4	ENST00000331134.11	TSL:1 MANE Select	c.36G>C	p.Pro12Pro	synonymous	Exon 2 of 17	ENSP00000331487.5	Q8TAT6-1
	NPLOC4	ENST00000705719.1		c.165G>C	p.Pro55Pro	synonymous	Exon 2 of 17	ENSP00000516165.1	A0A994J7H4
	NPLOC4	ENST00000374747.9	TSL:2	c.36G>C	p.Pro12Pro	synonymous	Exon 2 of 16	ENSP00000363879.5	Q8TAT6-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	0.83
DANN	Benign	0.65
PhyloP100		-3.3
PromoterAI		-0.078	Neutral

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: rs9894429; hg19: chr17-79596811;