NM_016525.5:c.287C>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_016525.5(UBAP1):c.287C>T(p.Pro96Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000745 in 1,515,954 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 0.00045 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

UBAP1
NM_016525.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.79

Publications

1 publications found

Variant links:

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)

UBAP1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.035039335).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000454 (69/152132) while in subpopulation AFR AF = 0.00155 (64/41412). AF 95% confidence interval is 0.00124. There are 0 homozygotes in GnomAd4. There are 37 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 69 Unknown,AD gene.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBAP1	NM_016525.5	MANE Select	c.287C>T	p.Pro96Leu	missense	Exon 4 of 7	NP_057609.2
UBAP1	NM_001171201.1		c.479C>T	p.Pro160Leu	missense	Exon 3 of 6	NP_001164672.1	Q9NZ09-4
UBAP1	NM_001171202.1		c.395C>T	p.Pro132Leu	missense	Exon 3 of 6	NP_001164673.1	Q9NZ09-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBAP1	ENST00000297661.9	TSL:1 MANE Select	c.287C>T	p.Pro96Leu	missense	Exon 4 of 7	ENSP00000297661.4	Q9NZ09-1
UBAP1	ENST00000359544.2	TSL:1	c.287C>T	p.Pro96Leu	missense	Exon 4 of 7	ENSP00000352541.2	Q9NZ09-1
UBAP1	ENST00000625521.2	TSL:2	c.479C>T	p.Pro160Leu	missense	Exon 3 of 6	ENSP00000486574.1	Q9NZ09-4

Frequencies

GnomAD3 genomes

AF:

0.000454

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00155

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000112

AC:

AN:

177954

AF XY:

0.0000749

show subpopulations

Gnomad AFR exome

AF:

0.00104

Gnomad AMR exome

AF:

0.0000478

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000231

Gnomad OTH exome

AF:

0.000246

GnomAD4 exome

AF:

0.0000323

AC:

AN:

1363822

Hom.:

Cov.:

AF XY:

0.0000374

AC XY:

AN XY:

667770

show subpopulations

African (AFR)

AF:

0.00116

AC:

AN:

30204

American (AMR)

AF:

0.0000689

AC:

AN:

29032

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19904

East Asian (EAS)

AF:

0.00

AC:

AN:

38870

South Asian (SAS)

AF:

0.0000145

AC:

AN:

68896

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49804

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5304

European-Non Finnish (NFE)

AF:

0.00000188

AC:

AN:

1065692

Other (OTH)

AF:

0.0000713

AC:

AN:

56116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000454

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.00155

AC:

AN:

41412

American (AMR)

AF:

0.000196

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5194

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.0000294

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000678

Hom.:

Bravo

AF:

0.000514

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000849

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.49

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.093

Eigen

Uncertain

0.19

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.82

M_CAP

Benign

0.0069

MetaRNN

Benign

0.035

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.97

PhyloP100

3.8

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.0

REVEL

Benign

0.095

Sift

Benign

0.12

Sift4G

Benign

0.36

Polyphen

0.010

Vest4

0.20

MVP

0.13

ClinPred

0.011

GERP RS

6.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.047

gMVP

0.52

Mutation Taster

=78/22

polymorphism

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over