NM_016525.5:c.-61C>T

Variant names:

• chr9-34179187-C-T
• rs988815377
• NM_016525.5:c.-61C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_016525.5(UBAP1):​c.-61C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000488 in 1,230,742 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 Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: UBAP1 NM_016525.5 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.332
• 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: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.10535854).

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.-61C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	NP_057609.2
	UBAP1	NM_016525.5	MANE Select	c.-61C>T		5_prime_UTR	Exon 1 of 7	NP_057609.2
	UBAP1	NM_001171203.3		c.-216C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 8	NP_001164674.1	Q9NZ09-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAP1	ENST00000297661.9	TSL:1 MANE Select	c.-61C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 7	ENSP00000297661.4	Q9NZ09-1
	UBAP1	ENST00000297661.9	TSL:1 MANE Select	c.-61C>T		5_prime_UTR	Exon 1 of 7	ENSP00000297661.4	Q9NZ09-1
	UBAP1	ENST00000965874.1		c.-177C>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 9	ENSP00000635933.1

Frequencies

GnomAD3 genomes AF: 0.0000199 AC: 3 AN: 150760 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000278 AC: 3 AN: 1079982 Hom.: 0 Cov.: 33 AF XY: 0.00000196 AC XY: 1 AN XY: 510546

African (AFR) AF: 0.00 AC: 0 AN: 22906

American (AMR) AF: 0.00 AC: 0 AN: 8278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 14206

East Asian (EAS) AF: 0.00 AC: 0 AN: 26276

South Asian (SAS) AF: 0.00 AC: 0 AN: 20780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 22176

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3898

European-Non Finnish (NFE) AF: 0.00000327 AC: 3 AN: 917962

Other (OTH) AF: 0.00 AC: 0 AN: 43500

GnomAD4 genome AF: 0.0000199 AC: 3 AN: 150760 Hom.: 0 Cov.: 31 AF XY: 0.0000272 AC XY: 2 AN XY: 73566

African (AFR) AF: 0.00 AC: 0 AN: 41058

American (AMR) AF: 0.00 AC: 0 AN: 15106

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3456

East Asian (EAS) AF: 0.00 AC: 0 AN: 5064

South Asian (SAS) AF: 0.00 AC: 0 AN: 4680

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10356

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000443 AC: 3 AN: 67738

Other (OTH) AF: 0.00 AC: 0 AN: 2082

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.59
CADD	Benign	17
DANN	Uncertain	0.99
DEOGEN2	Benign	0.010	T
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.57
FATHMM_MKL	Benign	0.23	N
LIST_S2	Benign	0.55	T
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.33
PrimateAI	Uncertain	0.50	T
Sift4G	Pathogenic	0.0	D
Vest4		0.13
MVP		0.043
ClinPred		0.92	D
GERP RS		2.4
PromoterAI		-0.048	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.1
gMVP		0.21
Mutation Taster		=90/10	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: rs988815377; hg19: chr9-34179185; COSMIC: COSV52657741;