9-34179081-G-C

Variant names:

• chr9-34179081-G-C
• rs756968108
• NM_016525.5:c.-167G>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BS1 BS2

The NM_001171201.1(UBAP1):​c.67G>C​(p.Gly23Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000704 in 1,277,884 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G23S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: UBAP1 NM_001171201.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0930
• 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: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.08114937).
• BS1: Variant frequency is greater than expected in population afr. GnomAdExome4 allele frequency = 0.00000711 (8/1125748) while in subpopulation AFR AF = 0.000253 (6/23752). AF 95% confidence interval is 0.000109. There are 0 homozygotes in GnomAdExome4. There are 6 alleles in the male GnomAdExome4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAdExome4 at 8 AD,Unknown gene.

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.-167G>C		5_prime_UTR	Exon 1 of 7	NP_057609.2
	UBAP1	NM_001171201.1		c.67G>C	p.Gly23Arg	missense	Exon 1 of 6	NP_001164672.1	Q9NZ09-4
	UBAP1	NM_001171202.1		c.67G>C	p.Gly23Arg	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.-167G>C		5_prime_UTR	Exon 1 of 7	ENSP00000297661.4	Q9NZ09-1
	UBAP1	ENST00000625521.2	TSL:2	c.67G>C	p.Gly23Arg	missense	Exon 1 of 6	ENSP00000486574.1	Q9NZ09-4
	UBAP1	ENST00000626262.2	TSL:2	c.37G>C	p.Gly13Arg	missense	Exon 1 of 6	ENSP00000487222.1	A0A0D9SG79

Frequencies

GnomAD3 genomes AF: 0.00000657 AC: 1 AN: 152136 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000241

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: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000711 AC: 8 AN: 1125748 Hom.: 0 Cov.: 33 AF XY: 0.0000111 AC XY: 6 AN XY: 540338

African (AFR) AF: 0.000253 AC: 6 AN: 23752

American (AMR) AF: 0.00 AC: 0 AN: 10940

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 15192

East Asian (EAS) AF: 0.00 AC: 0 AN: 27130

South Asian (SAS) AF: 0.00 AC: 0 AN: 32650

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 24028

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4618

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 942052

Other (OTH) AF: 0.0000441 AC: 2 AN: 45386

GnomAD4 genome AF: 0.00000657 AC: 1 AN: 152136 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74322

African (AFR) AF: 0.0000241 AC: 1 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15250

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10616

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68016

Other (OTH) AF: 0.00 AC: 0 AN: 2092

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	0.21
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0067	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.67
FATHMM_MKL	Benign	0.028	N
LIST_S2	Benign	0.48	T
M_CAP	Benign	0.0043	T
MetaRNN	Benign	0.081	T
MetaSVM	Benign	-1.1	T
PhyloP100		0.093
PrimateAI	Benign	0.42	T
Sift4G	Pathogenic	0.0	D
Vest4		0.35
MVP		0.043
ClinPred		0.88	D
GERP RS		-0.44
PromoterAI		-0.021	Neutral
gMVP		0.029
Mutation Taster		=86/14	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: rs756968108; hg19: chr9-34179079;