rs10971977

Variant names:

• chr9-34180025-A-T
• rs10971977
• NM_016525.5:c.-8+785A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016525.5(UBAP1):​c.-8+785A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 152,132 control chromosomes in the GnomAD database, including 9,823 homozygotes. 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: 𝑓 0.32 (9823 hom., cov: 32)
• Consequence: UBAP1 NM_016525.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0670
• Publications: 2 publications found

Genes affected

UBAP1 (HGNC:12461): (ubiquitin associated protein 1) This gene is a member of the UBA domain family, whose members include proteins having connections to ubiquitin and the ubiquitination pathway. The ubiquitin associated domain is thought to be a non-covalent ubiquitin binding domain consisting of a compact three helix bundle. This particular protein originates from a gene locus in a refined region on chromosome 9 undergoing loss of heterozygosity in nasopharyngeal carcinoma (NPC). Taking into account its cytogenetic location, this UBA domain family member is being studies as a putative target for mutation in nasopharyngeal carcinomas. Multiple alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2010]

UBAP1 Gene-Disease associations (from GenCC):

• spastic paraplegia 80, autosomal dominant

  Inheritance: AD Classification: STRONG Submitted by: Illumina, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• hereditary spastic paraplegia 12

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Tourette syndrome

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP1	NM_016525.5	c.-8+785A>T		intron_variant	Intron 1 of 6	ENST00000297661.9	NP_057609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAP1	ENST00000297661.9	c.-8+785A>T		intron_variant	Intron 1 of 6	1	NM_016525.5	ENSP00000297661.4
UBAP1	ENST00000625521.2	c.226+785A>T		intron_variant	Intron 1 of 5	2		ENSP00000486574.1
UBAP1	ENST00000626262.2	c.196+785A>T		intron_variant	Intron 1 of 5	2		ENSP00000487222.1
UBAP1	ENST00000379186.8	c.-8+785A>T		intron_variant	Intron 1 of 5	5		ENSP00000368484.3

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49358 AN: 152014 Hom.: 9824 Cov.: 32

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.551

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.0593

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.417

Gnomad MID AF: 0.323

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.345

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.324 AC: 49347 AN: 152132 Hom.: 9823 Cov.: 32 AF XY: 0.322 AC XY: 23940 AN XY: 74368

African (AFR) AF: 0.119 AC: 4928 AN: 41534

American (AMR) AF: 0.334 AC: 5101 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.362 AC: 1256 AN: 3472

East Asian (EAS) AF: 0.0595 AC: 308 AN: 5178

South Asian (SAS) AF: 0.329 AC: 1587 AN: 4826

European-Finnish (FIN) AF: 0.417 AC: 4405 AN: 10564

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30449 AN: 67982

Other (OTH) AF: 0.342 AC: 721 AN: 2110

Alfa AF: 0.376 Hom.: 1463

Bravo AF: 0.305

Asia WGS AF: 0.206 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.59
PhyloP100		-0.067
Mutation Taster		=100/0	polymorphism (auto)

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: rs10971977; hg19: chr9-34180023; COSMIC: COSV52657923;