Genetic Variant UBAP1:c.-48C>G (chr9-34179200-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001171201.1(UBAP1):c.186C>G(p.Ser62Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBAP1
NM_001171201.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0530

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14186686).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP1	NM_016525.5 link	c.-48C>G		5_prime_UTR_variant	Exon 1 of 7	ENST00000297661.9	NP_057609.2	Q9NZ09-1A0A6G6AA68

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBAP1	ENST00000297661 link	c.-48C>G		5_prime_UTR_variant	Exon 1 of 7	1	NM_016525.5	ENSP00000297661.4	Q9NZ09-1
UBAP1	ENST00000625521.2 link	c.186C>G	p.Ser62Arg	missense_variant	Exon 1 of 6	2		ENSP00000486574.1	Q9NZ09-4
UBAP1	ENST00000626262.2 link	c.156C>G	p.Ser52Arg	missense_variant	Exon 1 of 6	2		ENSP00000487222.1	A0A0D9SG79
UBAP1	ENST00000379186 link	c.-48C>G		5_prime_UTR_variant	Exon 1 of 6	5		ENSP00000368484.3	Q9NZ09-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1083178

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

511812

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Jan 27, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.186C>G (p.S62R) alteration is located in exon 1 (coding exon 1) of the UBAP1 gene. This alteration results from a C to G substitution at nucleotide position 186, causing the serine (S) at amino acid position 62 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Benign

0.015

.;T

Eigen

Benign

-0.60

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.55

LIST_S2

Benign

0.38

T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.14

T;T

MetaSVM

Benign

-1.1

PrimateAI

Uncertain

0.62

Sift4G

Pathogenic

0.0

D;D

Vest4

0.19

MVP

0.043

ClinPred

0.78

GERP RS

1.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.16

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over