16-680226-G-C

Position:

• chr16-680226-G-C

Variant summary

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

The ENST00000565677.5(STUB1):​c.-605G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 159,464 control chromosomes in the GnomAD database, including 68 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (68 hom., cov: 32)
  • Exomes 𝑓: 0.0019 (0 hom.)
• Consequence: STUB1 ENST00000565677.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0490

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 16-680226-G-C is Benign according to our data. Variant chr16-680226-G-C is described in ClinVar as [Benign]. Clinvar id is 1231278.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STUB1	ENST00000565677.5	c.-605G>C		5_prime_UTR_variant	1/7	1		ENSP00000457228

Frequencies

GnomAD3 genomes AF: 0.0154 AC: 2338 AN: 152162 Hom.: 68 Cov.: 32

Gnomad AFR AF: 0.0528

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00765

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00956

GnomAD4 exome AF: 0.00195 AC: 14 AN: 7194 Hom.: 0 Cov.: 0 AF XY: 0.00195 AC XY: 8 AN XY: 4102

Gnomad4 AFR exome AF: 0.0797

Gnomad4 AMR exome AF: 0.00820

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00235

GnomAD4 genome AF: 0.0153 AC: 2335 AN: 152270 Hom.: 68 Cov.: 32 AF XY: 0.0147 AC XY: 1097 AN XY: 74458

Gnomad4 AFR AF: 0.0526

Gnomad4 AMR AF: 0.00764

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.0125 Hom.: 6

Bravo AF: 0.0178

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 18, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	5.1
DANN	Benign	0.37

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs116166850; hg19: chr16-730226;