rs557232092

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr16-680430-C-T
• chr16-680430-C-A
• chr16-680430-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_005861.4(STUB1):​c.-96C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00179 in 1,086,602 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0086 (17 hom., cov: 32)
  • Exomes 𝑓: 0.00070 (9 hom.)
• Consequence: STUB1 NM_005861.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.778
• Publications: 1 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: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 16-680430-C-T is Benign according to our data. Variant chr16-680430-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1723009.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00855 (1292/151024) while in subpopulation AFR AF = 0.029 (1198/41352). AF 95% confidence interval is 0.0276. There are 17 homozygotes in GnomAd4. There are 609 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 17 AD,AR gene

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>T		5_prime_UTR	Exon 1 of 7	NP_005852.2	Q9UNE7-1
	STUB1	NM_001293197.2		c.-401C>T		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>T		5_prime_UTR	Exon 1 of 7	ENSP00000219548.4	Q9UNE7-1
	STUB1	ENST00000565677.5	TSL:1	c.-401C>T		5_prime_UTR	Exon 1 of 7	ENSP00000457228.1	Q9UNE7-2
	STUB1	ENST00000965393.1		c.-96C>T		5_prime_UTR	Exon 1 of 7	ENSP00000635452.1

Frequencies

GnomAD3 genomes AF: 0.00858 AC: 1295 AN: 150918 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0291

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00482

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000133

Gnomad OTH AF: 0.00483

GnomAD4 exome AF: 0.000699 AC: 654 AN: 935578 Hom.: 9 Cov.: 15 AF XY: 0.000605 AC XY: 267 AN XY: 441218

African (AFR) AF: 0.0294 AC: 542 AN: 18464

American (AMR) AF: 0.00328 AC: 17 AN: 5178

Ashkenazi Jewish (ASJ) AF: 0.000102 AC: 1 AN: 9806

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

South Asian (SAS) AF: 0.0000570 AC: 1 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: 0.0000405 AC: 33 AN: 815008

Other (OTH) AF: 0.00172 AC: 60 AN: 34954

GnomAD4 genome AF: 0.00855 AC: 1292 AN: 151024 Hom.: 17 Cov.: 32 AF XY: 0.00825 AC XY: 609 AN XY: 73786

African (AFR) AF: 0.0290 AC: 1198 AN: 41352

American (AMR) AF: 0.00481 AC: 73 AN: 15176

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5092

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10144

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000133 AC: 9 AN: 67674

Other (OTH) AF: 0.00478 AC: 10 AN: 2094

Alfa AF: 0.00112 Hom.: 0

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Benign	0.93
PhyloP100		-0.78
PromoterAI		-0.067	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=300/0	polymorphism

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;