16-680830-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_005861.4(STUB1):c.159+146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 751,636 control chromosomes in the GnomAD database, including 24,957 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.25 (5595 hom., cov: 27)
  • Exomes 𝑓: 0.23 (19362 hom.)
• Consequence: STUB1 NM_005861.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.959

Genes affected

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 16-680830-C-T is Benign according to our data. Variant chr16-680830-C-T is described in ClinVar as [Benign]. Clinvar id is 1295562.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.678 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STUB1	NM_005861.4	c.159+146C>T		intron_variant		ENST00000219548.9
STUB1	NM_001293197.2	c.-147+146C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STUB1	ENST00000219548.9	c.159+146C>T		intron_variant		1	NM_005861.4	P1

Frequencies

GnomAD3 genomes AF: 0.254 AC: 37372 AN: 147116 Hom.: 5590 Cov.: 27

Gnomad AFR AF: 0.175

Gnomad AMI AF: 0.196

Gnomad AMR AF: 0.355

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.419

Gnomad FIN AF: 0.341

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.233 AC: 140895 AN: 604420 Hom.: 19362 Cov.: 9 AF XY: 0.234 AC XY: 68682 AN XY: 293394

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.402

Gnomad4 ASJ exome AF: 0.231

Gnomad4 EAS exome AF: 0.694

Gnomad4 SAS exome AF: 0.394

Gnomad4 FIN exome AF: 0.370

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.253

GnomAD4 genome AF: 0.254 AC: 37400 AN: 147216 Hom.: 5595 Cov.: 27 AF XY: 0.266 AC XY: 19095 AN XY: 71764

Gnomad4 AFR AF: 0.175

Gnomad4 AMR AF: 0.355

Gnomad4 ASJ AF: 0.234

Gnomad4 EAS AF: 0.698

Gnomad4 SAS AF: 0.418

Gnomad4 FIN AF: 0.341

Gnomad4 NFE AF: 0.225

Gnomad4 OTH AF: 0.244

Alfa AF: 0.132 Hom.: 264

Bravo AF: 0.248

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

GeneDx

Sep 25, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	2.1
Dann	Benign	0.92

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: rs78410329; hg19: chr16-730830;