9-34241329-A-T

Variant names:

• chr9-34241329-A-T
• rs758296334
• NM_016525.5:c.304A>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_016525.5(UBAP1):​c.304A>T​(p.Met102Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000733 in 1,365,178 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: UBAP1 NM_016525.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.39
• 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)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07258129).

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.304A>T	p.Met102Leu	missense	Exon 4 of 7	NP_057609.2
	UBAP1	NM_001171201.1		c.496A>T	p.Met166Leu	missense	Exon 3 of 6	NP_001164672.1	Q9NZ09-4
	UBAP1	NM_001171202.1		c.412A>T	p.Met138Leu	missense	Exon 3 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.304A>T	p.Met102Leu	missense	Exon 4 of 7	ENSP00000297661.4	Q9NZ09-1
	UBAP1	ENST00000359544.2	TSL:1	c.304A>T	p.Met102Leu	missense	Exon 4 of 7	ENSP00000352541.2	Q9NZ09-1
	UBAP1	ENST00000625521.2	TSL:2	c.496A>T	p.Met166Leu	missense	Exon 3 of 6	ENSP00000486574.1	Q9NZ09-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.33e-7 AC: 1 AN: 1365178 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 668596

African (AFR) AF: 0.00 AC: 0 AN: 30242

American (AMR) AF: 0.00 AC: 0 AN: 29234

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19932

East Asian (EAS) AF: 0.00 AC: 0 AN: 38890

South Asian (SAS) AF: 0.00 AC: 0 AN: 69530

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49846

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5308

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1066040

Other (OTH) AF: 0.0000178 AC: 1 AN: 56156

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Spastic paraplegia 80, autosomal dominant (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	14
DANN	Benign	0.85
DEOGEN2	Benign	0.053	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.32
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.073	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.20	N
PhyloP100		3.4
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.034
Sift	Benign	0.66	T
Sift4G	Benign	0.40	T
Polyphen		0.0040	B
Vest4		0.30
MutPred		0.11		Loss of methylation at K106 (P = 0.059)
MVP		0.16
ClinPred		0.18	T
GERP RS		2.9
Varity_R		0.046
gMVP		0.16
Mutation Taster		=95/5	polymorphism

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: rs758296334; hg19: chr9-34241327;