16-681771-C-T

Position:

• chr16-681771-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001005920.4(JMJD8):​c.*1023G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0336 in 1,579,478 control chromosomes in the GnomAD database, including 1,187 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.049 (305 hom., cov: 34)
  • Exomes 𝑓: 0.032 (882 hom.)
• Consequence: JMJD8 NM_001005920.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.155

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 Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 16-681771-C-T is Benign according to our data. Variant chr16-681771-C-T is described in ClinVar as [Benign]. Clinvar id is 1236838.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0998 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
JMJD8	NM_001005920.4	c.*1023G>A		3_prime_UTR_variant	9/9	ENST00000609261.6	NP_001005920.3
STUB1	NM_005861.4	c.525-22C>T		intron_variant		ENST00000219548.9	NP_005852.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
JMJD8	ENST00000609261.6	c.*1023G>A		3_prime_UTR_variant	9/9	1	NM_001005920.4	ENSP00000477481	P1
STUB1	ENST00000219548.9	c.525-22C>T		intron_variant		1	NM_005861.4	ENSP00000219548	P1

Frequencies

GnomAD3 genomes AF: 0.0490 AC: 7453 AN: 152216 Hom.: 307 Cov.: 34

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.0298

Gnomad ASJ AF: 0.0300

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.0292

Gnomad FIN AF: 0.0229

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0296

Gnomad OTH AF: 0.0412

GnomAD3 exomes AF: 0.0321 AC: 7425 AN: 231024 Hom.: 196 AF XY: 0.0312 AC XY: 3895 AN XY: 124792

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.0194

Gnomad ASJ exome AF: 0.0305

Gnomad EAS exome AF: 0.0193

Gnomad SAS exome AF: 0.0347

Gnomad FIN exome AF: 0.0215

Gnomad NFE exome AF: 0.0291

Gnomad OTH exome AF: 0.0318

GnomAD4 exome AF: 0.0319 AC: 45556 AN: 1427144 Hom.: 882 Cov.: 32 AF XY: 0.0319 AC XY: 22469 AN XY: 704866

Gnomad4 AFR exome AF: 0.103

Gnomad4 AMR exome AF: 0.0208

Gnomad4 ASJ exome AF: 0.0296

Gnomad4 EAS exome AF: 0.0355

Gnomad4 SAS exome AF: 0.0335

Gnomad4 FIN exome AF: 0.0231

Gnomad4 NFE exome AF: 0.0303

Gnomad4 OTH exome AF: 0.0335

GnomAD4 genome AF: 0.0490 AC: 7457 AN: 152334 Hom.: 305 Cov.: 34 AF XY: 0.0475 AC XY: 3539 AN XY: 74490

Gnomad4 AFR AF: 0.102

Gnomad4 AMR AF: 0.0297

Gnomad4 ASJ AF: 0.0300

Gnomad4 EAS AF: 0.0189

Gnomad4 SAS AF: 0.0292

Gnomad4 FIN AF: 0.0229

Gnomad4 NFE AF: 0.0296

Gnomad4 OTH AF: 0.0412

Alfa AF: 0.0344 Hom.: 63

Bravo AF: 0.0519

Asia WGS AF: 0.0620 AC: 216 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 15, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.0
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs1046112; hg19: chr16-731771;