9-34179102-G-T

Variant names:

• chr9-34179102-G-T
• rs1445642401
• NM_016525.5:c.-146G>T

Variant summary

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

The NM_001171201.1(UBAP1):​c.88G>T​(p.Ala30Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000234 in 1,279,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000018 (0 hom.)
• Consequence: UBAP1 NM_001171201.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.70
• 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)

ENSG00000306290 (HGNC:):

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=0.18527582).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001171201.1. 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.-146G>T		5_prime_UTR	Exon 1 of 7	NP_057609.2
	UBAP1	NM_001171201.1		c.88G>T	p.Ala30Ser	missense	Exon 1 of 6	NP_001164672.1	Q9NZ09-4
	UBAP1	NM_001171202.1		c.88G>T	p.Ala30Ser	missense	Exon 1 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.-146G>T		5_prime_UTR	Exon 1 of 7	ENSP00000297661.4	Q9NZ09-1
	UBAP1	ENST00000625521.2	TSL:2	c.88G>T	p.Ala30Ser	missense	Exon 1 of 6	ENSP00000486574.1	Q9NZ09-4
	UBAP1	ENST00000626262.2	TSL:2	c.58G>T	p.Ala20Ser	missense	Exon 1 of 6	ENSP00000487222.1	A0A0D9SG79

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 152090 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: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000177 AC: 2 AN: 1127664 Hom.: 0 Cov.: 33 AF XY: 0.00000185 AC XY: 1 AN XY: 541538

African (AFR) AF: 0.00 AC: 0 AN: 23762

American (AMR) AF: 0.00 AC: 0 AN: 10984

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15236

East Asian (EAS) AF: 0.0000736 AC: 2 AN: 27188

South Asian (SAS) AF: 0.00 AC: 0 AN: 33288

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4586

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 943060

Other (OTH) AF: 0.00 AC: 0 AN: 45456

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 152090 Hom.: 0 Cov.: 31 AF XY: 0.0000135 AC XY: 1 AN XY: 74290

African (AFR) AF: 0.00 AC: 0 AN: 41418

American (AMR) AF: 0.00 AC: 0 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5186

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68012

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.0000712 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	0.081
BayesDel_addAF	Benign	-0.093	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	20
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0071	T
Eigen	Benign	0.00040
Eigen_PC	Benign	0.13
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.018	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.98	T
PhyloP100		3.7
PrimateAI	Benign	0.45	T
Sift4G	Pathogenic	0.0	D
Vest4		0.41
MVP		0.068
ClinPred		0.99	D
GERP RS		4.3
PromoterAI		-0.030	Neutral
gMVP		0.052
Mutation Taster		=87/13	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: rs1445642401; hg19: chr9-34179100;