chr9-34249206-G-A

Variant names:

• chr9-34249206-G-A
• rs2380925
• NM_016525.5:c.1084-573G>A

Variant summary

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

The NM_016525.5(UBAP1):​c.1084-573G>A 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 151,982 control chromosomes in the GnomAD database, including 9,804 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 (9804 hom., cov: 31)
• Consequence: UBAP1 NM_016525.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.608
• Publications: 9 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=-0.81).
• 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.1084-573G>A		intron_variant	Intron 4 of 6	ENST00000297661.9	NP_057609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAP1	ENST00000297661.9	c.1084-573G>A		intron_variant	Intron 4 of 6	1	NM_016525.5	ENSP00000297661.4

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49299 AN: 151864 Hom.: 9805 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.334

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.0596

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.448

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.324 AC: 49288 AN: 151982 Hom.: 9804 Cov.: 31 AF XY: 0.322 AC XY: 23898 AN XY: 74266

African (AFR) AF: 0.118 AC: 4910 AN: 41486

American (AMR) AF: 0.334 AC: 5102 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1268 AN: 3468

East Asian (EAS) AF: 0.0597 AC: 309 AN: 5172

South Asian (SAS) AF: 0.327 AC: 1576 AN: 4818

European-Finnish (FIN) AF: 0.416 AC: 4390 AN: 10542

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30427 AN: 67916

Other (OTH) AF: 0.341 AC: 720 AN: 2110

Alfa AF: 0.411 Hom.: 8599

Bravo AF: 0.305

Asia WGS AF: 0.206 AC: 720 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.77
PhyloP100		0.61
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: rs2380925; hg19: chr9-34249204; COSMIC: COSV52658093; COSMIC: COSV52658093;