rs12375731

Variant names:

• chr9-34204268-G-A
• rs12375731
• NM_016525.5:c.-7-16640G>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.-7-16640G>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 152,098 control chromosomes in the GnomAD database, including 9,820 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 (9820 hom., cov: 33)
• Consequence: UBAP1 NM_016525.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0730
• Publications: 3 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: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016525.5. 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
	UBAP1	NM_016525.5	MANE Select	c.-7-16640G>A		intron	N/A	NP_057609.2
	UBAP1	NM_001171201.1		c.226+25028G>A		intron	N/A	NP_001164672.1	Q9NZ09-4
	UBAP1	NM_001171202.1		c.227-16640G>A		intron	N/A	NP_001164673.1	Q9NZ09-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAP1	ENST00000297661.9	TSL:1 MANE Select	c.-7-16640G>A		intron	N/A	ENSP00000297661.4	Q9NZ09-1
	UBAP1	ENST00000625521.2	TSL:2	c.226+25028G>A		intron	N/A	ENSP00000486574.1	Q9NZ09-4
	UBAP1	ENST00000626262.2	TSL:2	c.197-16640G>A		intron	N/A	ENSP00000487222.1	A0A0D9SG79

Frequencies

GnomAD3 genomes AF: 0.325 AC: 49362 AN: 151982 Hom.: 9821 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.548

Gnomad AMR AF: 0.335

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.0593

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.320

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: 49350 AN: 152098 Hom.: 9820 Cov.: 33 AF XY: 0.322 AC XY: 23940 AN XY: 74366

African (AFR) AF: 0.119 AC: 4931 AN: 41530

American (AMR) AF: 0.335 AC: 5113 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1266 AN: 3468

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

South Asian (SAS) AF: 0.328 AC: 1585 AN: 4826

European-Finnish (FIN) AF: 0.416 AC: 4394 AN: 10566

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.448 AC: 30443 AN: 67940

Other (OTH) AF: 0.341 AC: 721 AN: 2112

Alfa AF: 0.366 Hom.: 1469

Bravo AF: 0.306

Asia WGS AF: 0.205 AC: 718 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.3
DANN	Benign	0.65
PhyloP100		-0.073
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: rs12375731; hg19: chr9-34204266; COSMIC: COSV52657994; COSMIC: COSV52657994;