chr16-680430-C-A

Variant names:

• chr16-680430-C-A
• rs557232092
• NM_005861.4:c.-96C>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_005861.4(STUB1):​c.-96C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000214 in 935,576 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: 0.0000021 (0 hom.)
• Consequence: STUB1 NM_005861.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.778
• Publications: 0 publications found

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

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005861.4. 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	NM_005861.4	MANE Select	c.-96C>A		5_prime_UTR	Exon 1 of 7	NP_005852.2	Q9UNE7-1
	STUB1	NM_001293197.2		c.-401C>A		5_prime_UTR	Exon 1 of 7	NP_001280126.1	Q9UNE7-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	STUB1	ENST00000219548.9	TSL:1 MANE Select	c.-96C>A		5_prime_UTR	Exon 1 of 7	ENSP00000219548.4	Q9UNE7-1
	STUB1	ENST00000565677.5	TSL:1	c.-401C>A		5_prime_UTR	Exon 1 of 7	ENSP00000457228.1	Q9UNE7-2
	STUB1	ENST00000965393.1		c.-96C>A		5_prime_UTR	Exon 1 of 7	ENSP00000635452.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000214 AC: 2 AN: 935576 Hom.: 0 Cov.: 15 AF XY: 0.00000227 AC XY: 1 AN XY: 441218

African (AFR) AF: 0.00 AC: 0 AN: 18466

American (AMR) AF: 0.00 AC: 0 AN: 5178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9806

East Asian (EAS) AF: 0.00 AC: 0 AN: 16720

South Asian (SAS) AF: 0.00 AC: 0 AN: 17540

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 15624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2284

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 815004

Other (OTH) AF: 0.0000572 AC: 2 AN: 34954

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	14
DANN	Benign	0.83
PhyloP100		-0.78
PromoterAI		-0.038	Neutral
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

Other links and lift over

dbSNP: rs557232092; hg19: chr16-730430;