16-680430-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005861.4(STUB1):c.-96C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,086,602 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0086 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (9 hom.)
• Consequence: STUB1 NM_005861.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.778

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=-0.68).
• BP6: Variant 16-680430-C-T is Benign according to our data. Variant chr16-680430-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1723009.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00855 (1292/151024) while in subpopulation AFR AF= 0.029 (1198/41352). AF 95% confidence interval is 0.0276. There are 17 homozygotes in gnomad4. There are 609 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 17 AD,AR,Digenic gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STUB1	NM_005861.4	c.-96C>T		5_prime_UTR_variant	1/7	ENST00000219548.9
STUB1	NM_001293197.2	c.-401C>T		5_prime_UTR_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STUB1	ENST00000219548.9	c.-96C>T		5_prime_UTR_variant	1/7	1	NM_005861.4	P1

Frequencies

GnomAD3 genomes AF: 0.00858 AC: 1295 AN: 150918 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00482

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00483

GnomAD4 exome AF: 0.000699 AC: 654 AN: 935578 Hom.: 9 Cov.: 15 AF XY: 0.000605 AC XY: 267 AN XY: 441218

Gnomad4 AFR exome AF: 0.0294

Gnomad4 AMR exome AF: 0.00328

Gnomad4 ASJ exome AF: 0.000102

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000570

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000405

Gnomad4 OTH exome AF: 0.00172

GnomAD4 genome AF: 0.00855 AC: 1292 AN: 151024 Hom.: 17 Cov.: 32 AF XY: 0.00825 AC XY: 609 AN XY: 73786

Gnomad4 AFR AF: 0.0290

Gnomad4 AMR AF: 0.00481

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000133

Gnomad4 OTH AF: 0.00478

Alfa AF: 0.00112 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

May 22, 2021

See Variant Classification Assertion Criteria. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	16
Dann	Benign	0.93
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: rs557232092; hg19: chr16-730430;