rs993140598

Variant names:

• chr9-34179074-C-T
• rs993140598
• NM_016525.5:c.-174C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_001171201.1(UBAP1):​c.60C>T​(p.Gly20Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000267 in 1,125,068 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0000027 (0 hom.)
• Consequence: UBAP1 NM_001171201.1 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.103
• Publications: 0 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)

ENSG00000306290 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 9-34179074-C-T is Benign according to our data. Variant chr9-34179074-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2659151.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.103 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171201.1. 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.-174C>T		5_prime_UTR	Exon 1 of 7	NP_057609.2
	UBAP1	NM_001171201.1		c.60C>T	p.Gly20Gly	synonymous	Exon 1 of 6	NP_001164672.1	Q9NZ09-4
	UBAP1	NM_001171202.1		c.60C>T	p.Gly20Gly	synonymous	Exon 1 of 6	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.-174C>T		5_prime_UTR	Exon 1 of 7	ENSP00000297661.4	Q9NZ09-1
	UBAP1	ENST00000625521.2	TSL:2	c.60C>T	p.Gly20Gly	synonymous	Exon 1 of 6	ENSP00000486574.1	Q9NZ09-4
	UBAP1	ENST00000626262.2	TSL:2	c.30C>T	p.Gly10Gly	synonymous	Exon 1 of 6	ENSP00000487222.1	A0A0D9SG79

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000267 AC: 3 AN: 1125068 Hom.: 0 Cov.: 33 AF XY: 0.00000370 AC XY: 2 AN XY: 539890

African (AFR) AF: 0.0000422 AC: 1 AN: 23690

American (AMR) AF: 0.00 AC: 0 AN: 10354

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15042

East Asian (EAS) AF: 0.00 AC: 0 AN: 27174

South Asian (SAS) AF: 0.0000309 AC: 1 AN: 32334

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24006

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4602

European-Non Finnish (NFE) AF: 0.00000106 AC: 1 AN: 942488

Other (OTH) AF: 0.00 AC: 0 AN: 45378

GnomAD4 genome Cov.: 31

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	-0.31
CADD	Benign	15
DANN	Benign	0.93
PhyloP100		-0.10
PromoterAI		-0.033	Neutral

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: rs993140598; hg19: chr9-34179072;