chr9-34179039-A-T

Variant names:

Variant summary

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

The NM_001171201.1(UBAP1):c.25A>T(p.Arg9Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 1,263,426 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0012 ( 2 hom. )

Consequence

UBAP1
NM_001171201.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2B:1

Conservation

PhyloP100: 1.34

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:

ENSG00000306290 (HGNC:):

ENSG00000306290 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=0.023744434).

BS1

Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.000329 (50/152104) while in subpopulation NFE AF = 0.000662 (45/67992). AF 95% confidence interval is 0.000508. There are 0 homozygotes in GnomAd4. There are 20 alleles in the male GnomAd4 subpopulation. Median coverage is 31. 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 50 Unknown,AD 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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBAP1	NM_001171201.1		c.25A>T	p.Arg9Trp	missense	Exon 1 of 6	NP_001164672.1	Q9NZ09-4
UBAP1	NM_001171202.1		c.25A>T	p.Arg9Trp	missense	Exon 1 of 6	NP_001164673.1	Q9NZ09-3
UBAP1	NM_016525.5	MANE Select	c.-209A>T		upstream_gene	N/A	NP_057609.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
UBAP1	ENST00000625521.2	TSL:2	c.25A>T	p.Arg9Trp	missense	Exon 1 of 6	ENSP00000486574.1	Q9NZ09-4
UBAP1	ENST00000859530.1		c.-307A>T		5_prime_UTR	Exon 1 of 8	ENSP00000529589.1
UBAP1	ENST00000859531.1		c.-325A>T		5_prime_UTR	Exon 1 of 8	ENSP00000529590.1

Frequencies

GnomAD3 genomes

AF:

0.000329

AC:

AN:

151986

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.000662

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000668

AC:

AN:

16458

AF XY:

0.000676

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00119

AC:

1327

AN:

1111322

Hom.:

Cov.:

AF XY:

0.00115

AC XY:

608

AN XY:

530384

show subpopulations

African (AFR)

AF:

0.000171

AC:

AN:

23446

American (AMR)

AF:

0.00

AC:

AN:

9608

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14738

East Asian (EAS)

AF:

0.00

AC:

AN:

26932

South Asian (SAS)

AF:

0.00

AC:

AN:

29846

European-Finnish (FIN)

AF:

0.00

AC:

AN:

23552

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4508

European-Non Finnish (NFE)

AF:

0.00137

AC:

1277

AN:

933890

Other (OTH)

AF:

0.00103

AC:

AN:

44802

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

136

203

271

339

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

116

174

232

290

<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:

0.000329

AC:

AN:

152104

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.000120

AC:

AN:

41494

American (AMR)

AF:

0.00

AC:

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10608

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000662

AC:

AN:

67992

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

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:

0.000714

Hom.:

Bravo

AF:

0.000442

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000519

AC:

ExAC

AF:

0.000291

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Spastic paraplegia 80, autosomal dominant (1)

UBAP1-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.44

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.65

M_CAP

Benign

0.019

MetaRNN

Benign

0.024

MetaSVM

Benign

-1.1

PhyloP100

1.3

PrimateAI

Uncertain

0.64

Sift4G

Pathogenic

0.0

Vest4

0.30

MVP

0.043

ClinPred

0.29

GERP RS

2.6

PromoterAI

-0.11

Neutral

(source)

gMVP

0.091

Mutation Taster

=69/31

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