NM_016525.5:c.34+5141G>C

Variant names:

• chr9-34226089-G-C
• rs10814079
• NM_016525.5:c.34+5141G>C

Variant summary

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

The NM_016525.5(UBAP1):​c.34+5141G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.359 in 141,696 control chromosomes in the GnomAD database, including 9,584 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 0.36 (9584 hom., cov: 27)
• Consequence: UBAP1 NM_016525.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0140
• Publications: 4 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.718 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAP1	NM_016525.5	MANE Select	c.34+5141G>C		intron	N/A	NP_057609.2
	UBAP1	NM_001171201.1		c.227-8127G>C		intron	N/A	NP_001164672.1
	UBAP1	NM_001171202.1		c.267+5141G>C		intron	N/A	NP_001164673.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAP1	ENST00000297661.9	TSL:1 MANE Select	c.34+5141G>C		intron	N/A	ENSP00000297661.4
	UBAP1	ENST00000359544.2	TSL:1	c.34+5141G>C		intron	N/A	ENSP00000352541.2
	UBAP1	ENST00000625521.2	TSL:2	c.227-8127G>C		intron	N/A	ENSP00000486574.1

Frequencies

GnomAD3 genomes AF: 0.359 AC: 50795 AN: 141578 Hom.: 9571 Cov.: 27

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.357

Gnomad AMR AF: 0.419

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.738

Gnomad SAS AF: 0.542

Gnomad FIN AF: 0.375

Gnomad MID AF: 0.486

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.377

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

GnomAD4 genome AF: 0.359 AC: 50839 AN: 141696 Hom.: 9584 Cov.: 27 AF XY: 0.368 AC XY: 25330 AN XY: 68886

African (AFR) AF: 0.267 AC: 10275 AN: 38502

American (AMR) AF: 0.419 AC: 5913 AN: 14114

Ashkenazi Jewish (ASJ) AF: 0.354 AC: 1178 AN: 3330

East Asian (EAS) AF: 0.738 AC: 3722 AN: 5044

South Asian (SAS) AF: 0.544 AC: 2506 AN: 4608

European-Finnish (FIN) AF: 0.375 AC: 3413 AN: 9104

Middle Eastern (MID) AF: 0.496 AC: 137 AN: 276

European-Non Finnish (NFE) AF: 0.354 AC: 22643 AN: 63908

Other (OTH) AF: 0.382 AC: 753 AN: 1972

Alfa AF: 0.195 Hom.: 399

Bravo AF: 0.341

Asia WGS AF: 0.567 AC: 1900 AN: 3366

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.2
DANN	Benign	0.74
PhyloP100		0.014
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: rs10814079; hg19: chr9-34226087; COSMIC: COSV52661527; COSMIC: COSV52661527;