chr9-34251954-G-A

Variant names:

• chr9-34251954-G-A
• rs3135929
• NM_016525.5:c.*422G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016525.5(UBAP1):​c.*422G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: UBAP1 NM_016525.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.308
• Publications: 6 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP1	NM_016525.5	c.*422G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000297661.9	NP_057609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAP1	ENST00000297661.9	c.*422G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_016525.5	ENSP00000297661.4
UBAP1	ENST00000359544.2	c.*422G>A		3_prime_UTR_variant	Exon 7 of 7	1		ENSP00000352541.2
UBAP1	ENST00000379186.8	c.*422G>A		3_prime_UTR_variant	Exon 6 of 6	5		ENSP00000368484.3
UBAP1	ENST00000625521.2	c.*422G>A		downstream_gene_variant		2		ENSP00000486574.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 9718 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 5076

African (AFR) AF: 0.00 AC: 0 AN: 370

American (AMR) AF: 0.00 AC: 0 AN: 1092

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 270

East Asian (EAS) AF: 0.00 AC: 0 AN: 480

South Asian (SAS) AF: 0.00 AC: 0 AN: 538

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 672

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 36

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 5778

Other (OTH) AF: 0.00 AC: 0 AN: 482

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 1184

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.7
DANN	Benign	0.59
PhyloP100		0.31

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: rs3135929; hg19: chr9-34251952;