16-681889-G-GC

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_001005920.4(JMJD8):c.*904_*905insG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000951 in 1,612,950 control chromosomes in the GnomAD database, including 20 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0010 (20 hom.)
• Consequence: JMJD8 NM_001005920.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.79

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]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 16-681889-G-GC is Benign according to our data. Variant chr16-681889-G-GC is described in ClinVar as [Benign]. Clinvar id is 2070282.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
JMJD8	NM_001005920.4	c.*904_*905insG		3_prime_UTR_variant	9/9	ENST00000609261.6
STUB1	NM_005861.4	c.612+15dup		intron_variant		ENST00000219548.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
JMJD8	ENST00000609261.6	c.*904_*905insG		3_prime_UTR_variant	9/9	1	NM_001005920.4	P1
STUB1	ENST00000219548.9	c.612+15dup		intron_variant		1	NM_005861.4	P1

Frequencies

GnomAD3 genomes AF: 0.000283 AC: 43 AN: 152208 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00517

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.000478

GnomAD3 exomes AF: 0.00173 AC: 433 AN: 249630 Hom.: 4 AF XY: 0.00240 AC XY: 325 AN XY: 135384

Gnomad AFR exome AF: 0.0000621

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0120

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000436

Gnomad OTH exome AF: 0.00115

GnomAD4 exome AF: 0.00102 AC: 1491 AN: 1460624 Hom.: 20 Cov.: 33 AF XY: 0.00141 AC XY: 1024 AN XY: 726590

Gnomad4 AFR exome AF: 0.000269

Gnomad4 AMR exome AF: 0.000246

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000151

Gnomad4 SAS exome AF: 0.0117

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000353

Gnomad4 OTH exome AF: 0.000845

GnomAD4 genome AF: 0.000282 AC: 43 AN: 152326 Hom.: 0 Cov.: 34 AF XY: 0.000336 AC XY: 25 AN XY: 74484

Gnomad4 AFR AF: 0.0000240

Gnomad4 AMR AF: 0.0000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00518

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.000477 Hom.: 0

Bravo AF: 0.000230

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 15, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs544433451; hg19: chr16-731889;