NM_001005920.4:c.*875_*917delACACACACAGACCCACATGTGGGTGGGGGGCACCCTCACGTGC

Variant names:

• chr16-681876-AGCACGTGAGGGTGCCCCCCACCCACATGTGGGTCTGTGTGTGT-A
• NM_001005920.4:c.*875_*917delACACACACAGACCCACATGTGGGTGGGGGGCACCCTCACGTGC

Variant summary

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

The NM_001005920.4(JMJD8):​c.*875_*917delACACACACAGACCCACATGTGGGTGGGGGGCACCCTCACGTGC variant causes a 3 prime UTR change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 34)
• Consequence: JMJD8 NM_001005920.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.23
• 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: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
• autosomal recessive spinocerebellar ataxia 16

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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.*875_*917delACACACACAGACCCACATGTGGGTGGGGGGCACCCTCACGTGC		3_prime_UTR	Exon 9 of 9	NP_001005920.3	Q96S16-1
	STUB1	NM_005861.4	MANE Select	c.612+4_612+46delAGGGTGCCCCCCACCCACATGTGGGTCTGTGTGTGTGCACGTG		splice_region intron	N/A	NP_005852.2	Q9UNE7-1
	JMJD8	NM_001323918.3		c.*909_*951delACACACACAGACCCACATGTGGGTGGGGGGCACCCTCACGTGC		3_prime_UTR	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.*875_*917delACACACACAGACCCACATGTGGGTGGGGGGCACCCTCACGTGC		3_prime_UTR	Exon 9 of 9	ENSP00000477481.1	Q96S16-1
	STUB1	ENST00000219548.9	TSL:1 MANE Select	c.612+4_612+46delAGGGTGCCCCCCACCCACATGTGGGTCTGTGTGTGTGCACGTG		splice_region intron	N/A	ENSP00000219548.4	Q9UNE7-1
	STUB1	ENST00000565677.5	TSL:1	c.396+4_396+46delAGGGTGCCCCCCACCCACATGTGGGTCTGTGTGTGTGCACGTG		splice_region intron	N/A	ENSP00000457228.1	Q9UNE7-2

Frequencies

GnomAD3 genomes Cov.: 34

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 34

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Autosomal recessive spinocerebellar ataxia 16 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2

Splicing

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

Other links and lift over

hg19: chr16-731876;