STUB1 p.His184His

Variant names:

• chr16-681817-C-C
• NM_001005920.4:c.

Your query was ambiguous. Multiple possible variants found:

• chr16-681818--
• chr16-681820-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001005920.4(JMJD8):​c. variant causes a exon region change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 34)
• Consequence: JMJD8 NM_001005920.4 exon_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.33
• Publications: 0 publications found

Genes affected

JMJD8 (HGNC:14148): (jumonji domain containing 8) Involved in several processes, including positive regulation of I-kappaB kinase/NF-kappaB signaling; positive regulation of sprouting angiogenesis; and regulation of glycolytic process. Located in endoplasmic reticulum lumen and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

STUB1 (HGNC:11427): (STIP1 homology and U-box containing protein 1) This gene encodes a protein containing tetratricopeptide repeat and a U-box that functions as a ubiquitin ligase/cochaperone. The encoded protein binds to and ubiquitinates shock cognate 71 kDa protein (Hspa8) and DNA polymerase beta (Polb), among other targets. Mutations in this gene cause spinocerebellar ataxia, autosomal recessive 16. Alternative splicing results in multiple transcript variants. There is a pseudogene for this gene on chromosome 2. [provided by RefSeq, Jun 2014]

STUB1 Gene-Disease associations (from GenCC):

• spinocerebellar ataxia 48

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia, Ambry Genetics
• autosomal recessive spinocerebellar ataxia 16

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, PanelApp Australia

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005920.4. 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
	JMJD8	NM_001005920.4	MANE Select	c.		exon_region	Exon 9 of 9	NP_001005920.3	Q96S16-1
	JMJD8	NM_001005920.4	MANE Select	c.		3_prime_UTR	Exon 9 of 9	NP_001005920.3	Q96S16-1
	JMJD8	NM_001323918.3		c.		exon_region	Exon 9 of 9	NP_001310847.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	JMJD8	ENST00000609261.6	TSL:1 MANE Select	c.		exon_region	Exon 9 of 9	ENSP00000477481.1	Q96S16-1
	JMJD8	ENST00000609261.6	TSL:1 MANE Select	c.		3_prime_UTR	Exon 9 of 9	ENSP00000477481.1	Q96S16-1
	JMJD8	ENST00000567120.5	TSL:1	n.		exon_region	Exon 8 of 8

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr16-731817;