Variant 16-680636-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM1PM2

The ENST00000219548.9(STUB1):c.111C>G(p.Phe37Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

STUB1
ENST00000219548.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.914

Variant links:

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]

STUB1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM1

In a repeat TPR 1 (size 33) in uniprot entity CHIP_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in ENST00000219548.9

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
STUB1	NM_005861.4 linkuse as main transcript	c.111C>G	p.Phe37Leu	missense_variant	1/7	ENST00000219548.9	NP_005852.2
STUB1	NM_001293197.2 linkuse as main transcript	c.-195C>G		5_prime_UTR_variant	1/7		NP_001280126.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
STUB1	ENST00000219548.9 linkuse as main transcript	c.111C>G	p.Phe37Leu	missense_variant	1/7	1	NM_005861.4	ENSP00000219548	P1	Q9UNE7-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1205012

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

589066

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

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:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

GeneDx

Feb 26, 2024

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 32211513) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

1.0

BayesDel_addAF

Uncertain

0.049

BayesDel_noAF

Benign

-0.17

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Pathogenic

0.84

D;.

Eigen

Benign

0.012

Eigen_PC

Benign

-0.068

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.95

D;D

M_CAP

Pathogenic

0.97

MetaRNN

Uncertain

0.66

D;D

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.9

L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Pathogenic

0.95

PROVEAN

Pathogenic

-4.5

D;D

REVEL

Uncertain

0.38

Sift

Uncertain

0.0040

D;T

Sift4G

Uncertain

0.0080

D;D

Polyphen

1.0

D;.

Vest4

0.47

MutPred

0.53

Gain of catalytic residue at F37 (P = 0.0398);Gain of catalytic residue at F37 (P = 0.0398);

MVP

0.65

MPC

2.1

ClinPred

0.99

GERP RS

1.5

Varity_R

0.88

gMVP

0.70

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over