9-34251954-G-T

Variant names:

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

Variant summary

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

The NM_016525.5(UBAP1):​c.*422G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 161,796 control chromosomes in the GnomAD database, including 2,474 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 0.16 (2352 hom., cov: 32)
  • Exomes 𝑓: 0.14 (122 hom.)
• 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.235 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.159 AC: 24185 AN: 151976 Hom.: 2349 Cov.: 32

Gnomad AFR AF: 0.0685

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.145

Gnomad EAS AF: 0.0532

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.187

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.168

GnomAD4 exome AF: 0.137 AC: 1329 AN: 9702 Hom.: 122 Cov.: 0 AF XY: 0.140 AC XY: 709 AN XY: 5072

African (AFR) AF: 0.0243 AC: 9 AN: 370

American (AMR) AF: 0.134 AC: 146 AN: 1086

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 28 AN: 270

East Asian (EAS) AF: 0.0250 AC: 12 AN: 480

South Asian (SAS) AF: 0.178 AC: 96 AN: 538

European-Finnish (FIN) AF: 0.155 AC: 104 AN: 672

Middle Eastern (MID) AF: 0.111 AC: 4 AN: 36

European-Non Finnish (NFE) AF: 0.152 AC: 875 AN: 5768

Other (OTH) AF: 0.114 AC: 55 AN: 482

GnomAD4 genome AF: 0.159 AC: 24188 AN: 152094 Hom.: 2352 Cov.: 32 AF XY: 0.160 AC XY: 11864 AN XY: 74340

African (AFR) AF: 0.0683 AC: 2835 AN: 41502

American (AMR) AF: 0.162 AC: 2482 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.145 AC: 502 AN: 3468

East Asian (EAS) AF: 0.0535 AC: 277 AN: 5178

South Asian (SAS) AF: 0.246 AC: 1185 AN: 4810

European-Finnish (FIN) AF: 0.187 AC: 1978 AN: 10572

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14339 AN: 67970

Other (OTH) AF: 0.167 AC: 354 AN: 2114

Alfa AF: 0.169 Hom.: 1184

Bravo AF: 0.149

Asia WGS AF: 0.149 AC: 520 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.4
DANN	Benign	0.63
PhyloP100		0.31
Mutation Taster		=95/5	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: rs3135929; hg19: chr9-34251952; COSMIC: COSV52662118; COSMIC: COSV52662118;