rs1196295221

Variant names:

• chr9-34179202-C-A
• rs1196295221
• NM_016525.5:c.-46C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-34179202-C-A
• chr9-34179202-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_016525.5(UBAP1):​c.-46C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000185 in 1,082,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: UBAP1 NM_016525.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33
• 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: 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.27496934).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP1	NM_016525.5	c.-46C>A		5_prime_UTR_variant	Exon 1 of 7	ENST00000297661.9	NP_057609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAP1	ENST00000297661.9	c.-46C>A		5_prime_UTR_variant	Exon 1 of 7	1	NM_016525.5	ENSP00000297661.4
UBAP1	ENST00000625521.2	c.188C>A	p.Thr63Asn	missense_variant	Exon 1 of 6	2		ENSP00000486574.1
UBAP1	ENST00000626262.2	c.158C>A	p.Thr53Asn	missense_variant	Exon 1 of 6	2		ENSP00000487222.1
UBAP1	ENST00000379186.8	c.-46C>A		5_prime_UTR_variant	Exon 1 of 6	5		ENSP00000368484.3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000185 AC: 2 AN: 1082826 Hom.: 0 Cov.: 33 AF XY: 0.00000195 AC XY: 1 AN XY: 511626

African (AFR) AF: 0.00 AC: 0 AN: 23000

American (AMR) AF: 0.00 AC: 0 AN: 8424

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14392

East Asian (EAS) AF: 0.00 AC: 0 AN: 26534

South Asian (SAS) AF: 0.00 AC: 0 AN: 20034

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3714

European-Non Finnish (NFE) AF: 0.00000217 AC: 2 AN: 920526

Other (OTH) AF: 0.00 AC: 0 AN: 43770

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.19	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.96
DEOGEN2	Benign	0.010	.;T
Eigen	Benign	0.086
Eigen_PC	Benign	0.11
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.37	T;T
M_CAP	Uncertain	0.088	D
MetaRNN	Benign	0.27	T;T
MetaSVM	Benign	-0.82	T
PhyloP100		1.3
PrimateAI	Uncertain	0.67	T
Sift4G	Pathogenic	0.0	D;D
Vest4		0.31
MVP		0.093
ClinPred		0.84	D
GERP RS		4.7
PromoterAI		-0.0024	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
gMVP		0.29
Mutation Taster		=63/37	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: rs1196295221; hg19: chr9-34179200;