dbSNP rs12599315: STUB1-DT:n.17G>A (chr16-679831-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000567091.2(STUB1-DT):n.17G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.411 in 145,232 control chromosomes in the GnomAD database, including 12,607 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.41 ( 12597 hom., cov: 25)

Exomes 𝑓: 0.42 ( 10 hom. )

Consequence

STUB1-DT
ENST00000567091.2 non_coding_transcript_exon

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.399

Publications

3 publications found

Variant links:

Genes affected

STUB1-DT (HGNC:54519): (STUB1 divergent transcript)

STUB1-DT links:

ENSG00000294321 (HGNC:):

ENSG00000294321 links:

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]

STUB1 Gene-Disease associations (from GenCC):

spinocerebellar ataxia 48
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, PanelApp Australia, Labcorp Genetics (formerly Invitae)
autosomal recessive spinocerebellar ataxia 16
Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Orphanet, Labcorp Genetics (formerly Invitae)

STUB1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 16-679831-C-T is Benign according to our data. Variant chr16-679831-C-T is described in ClinVar as Benign. ClinVar VariationId is 1231549.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.698 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000567091.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STUB1-DT	NR_136337.1		n.-54G>A		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank
STUB1-DT	ENST00000567091.2	TSL:3	n.17G>A	non_coding_transcript_exon	Exon 1 of 4
STUB1-DT	ENST00000722589.1		n.1G>A	non_coding_transcript_exon	Exon 1 of 4
STUB1-DT	ENST00000722590.1		n.1G>A	non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

AF:

0.411

AC:

59621

AN:

145056

Hom.:

12585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.331

Gnomad EAS

AF:

0.719

Gnomad SAS

AF:

0.682

Gnomad FIN

AF:

0.462

Gnomad MID

AF:

0.311

Gnomad NFE

AF:

0.378

Gnomad OTH

AF:

0.364

GnomAD4 exome

AF:

0.420

AC:

AN:

Hom.:

AF XY:

0.500

AC XY:

AN XY:

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

1.00

AC:

AN:

South Asian (SAS)

AF:

0.650

AC:

AN:

European-Finnish (FIN)

AF:

0.500

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.175

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.537

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.411

AC:

59657

AN:

145144

Hom.:

12597

Cov.:

AF XY:

0.421

AC XY:

29742

AN XY:

70590

show subpopulations

African (AFR)

AF:

0.380

AC:

14895

AN:

39224

American (AMR)

AF:

0.454

AC:

6664

AN:

14684

Ashkenazi Jewish (ASJ)

AF:

0.331

AC:

1123

AN:

3390

East Asian (EAS)

AF:

0.719

AC:

3433

AN:

4778

South Asian (SAS)

AF:

0.683

AC:

3068

AN:

4492

European-Finnish (FIN)

AF:

0.462

AC:

4377

AN:

9468

Middle Eastern (MID)

AF:

0.304

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.378

AC:

24950

AN:

65938

Other (OTH)

AF:

0.371

AC:

747

AN:

2016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

1547

3094

4642

6189

7736

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

568

1136

1704

2272

2840

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.244

Hom.:

577

Bravo

AF:

0.399

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

5.3

(source)

DANN

Benign

0.73

PhyloP100

-0.40

PromoterAI

-0.023

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over