rs11558085

chr16-680620-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 4P and 1B. PM1 PM2 BP4

The NM_005861.4(STUB1):c.95A>G(p.Gln32Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000803 in 1,244,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 8.0e-7 (0 hom.)
• Consequence: STUB1 NM_005861.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.92

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 Uncertain_significance. Variant got 3 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 NM_005861.4
• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27419376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
STUB1	NM_005861.4	c.95A>G	p.Gln32Arg	missense_variant	1/7	ENST00000219548.9
STUB1	NM_001293197.2	c.-211A>G		5_prime_UTR_variant	1/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
STUB1	ENST00000219548.9	c.95A>G	p.Gln32Arg	missense_variant	1/7	1	NM_005861.4	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 8.03e-7 AC: 1 AN: 1244670 Hom.: 0 Cov.: 31 AF XY: 0.00000163 AC XY: 1 AN XY: 612918

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: 0.00000100

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.065	T
BayesDel_noAF	Benign	-0.14
Cadd	Uncertain	23
Dann	Benign	0.95
DEOGEN2	Uncertain	0.69	D;.
Eigen	Benign	-0.30
Eigen_PC	Benign	-0.16
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.93	D;D
M_CAP	Pathogenic	0.88	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.5	L;.
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-2.1	N;N
REVEL	Benign	0.25
Sift	Benign	0.070	T;T
Sift4G	Benign	0.17	T;D
Polyphen		0.051	B;.
Vest4		0.41
MutPred		0.24		Gain of MoRF binding (P = 0.0184);Gain of MoRF binding (P = 0.0184);
MVP		0.71
MPC		1.1
ClinPred		0.26	T
GERP RS		3.5
Varity_R		0.49
gMVP		0.45

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: rs11558085; hg19: chr16-730620;