chr9-34179067-G-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.53G>T(p.Gly18Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000328 in 1,279,204 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

UBAP1
NM_001171201.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.46

Publications

0 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=0.015628546).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000184 (28/152268) while in subpopulation AFR AF = 0.00065 (27/41552). AF 95% confidence interval is 0.000459. There are 0 homozygotes in GnomAd4. There are 17 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 28 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_016525.5	MANE Select	c.-181G>T		5_prime_UTR	Exon 1 of 7	NP_057609.2
UBAP1	NM_001171201.1		c.53G>T	p.Gly18Val	missense	Exon 1 of 6	NP_001164672.1	Q9NZ09-4
UBAP1	NM_001171202.1		c.53G>T	p.Gly18Val	missense	Exon 1 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.-181G>T		5_prime_UTR	Exon 1 of 7	ENSP00000297661.4	Q9NZ09-1
UBAP1	ENST00000625521.2	TSL:2	c.53G>T	p.Gly18Val	missense	Exon 1 of 6	ENSP00000486574.1	Q9NZ09-4
UBAP1	ENST00000626262.2	TSL:2	c.23G>T	p.Gly8Val	missense	Exon 1 of 6	ENSP00000487222.1	A0A0D9SG79

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152150

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000656

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

GnomAD2 exomes

AF:

0.000151

AC:

AN:

19912

AF XY:

0.000106

show subpopulations

Gnomad AFR exome

AF:

0.00112

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:

0.0000833

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000124

AC:

AN:

1126936

Hom.:

Cov.:

AF XY:

0.00000739

AC XY:

AN XY:

540952

show subpopulations

African (AFR)

AF:

0.000464

AC:

AN:

23732

American (AMR)

AF:

0.00

AC:

AN:

10436

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15046

East Asian (EAS)

AF:

0.00

AC:

AN:

27218

South Asian (SAS)

AF:

0.00

AC:

AN:

33000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

24044

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4624

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

943410

Other (OTH)

AF:

0.0000660

AC:

AN:

45426

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

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:

0.000184

AC:

AN:

152268

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

AN XY:

74448

show subpopulations

African (AFR)

AF:

0.000650

AC:

AN:

41552

American (AMR)

AF:

0.0000655

AC:

AN:

15270

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68028

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

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:

0.00

Hom.:

Bravo

AF:

0.000185

ExAC

AF:

0.0000848

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

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

0.12

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.0078

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.13

LIST_S2

Benign

0.49

M_CAP

Benign

0.021

MetaRNN

Benign

0.016

MetaSVM

Benign

-1.1

PhyloP100

1.5

PrimateAI

Uncertain

0.54

Sift4G

Pathogenic

0.0

Vest4

0.49

MVP

0.043

ClinPred

0.18

GERP RS

0.95

PromoterAI

-0.17

Neutral

(source)

gMVP

0.054

Mutation Taster

=77/23

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