9-34179144-C-G

Position:

chr9-34179144-C-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBS1_SupportingBS2

The NM_001171201.1(UBAP1):c.130C>G(p.Leu44Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000591 in 1,251,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

UBAP1
NM_001171201.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.237

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:

UBAP1 (HGNC:):

UBAP1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.23595214).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000289 (44/152234) while in subpopulation AFR AF= 0.00101 (42/41548). AF 95% confidence interval is 0.000768. There are 0 homozygotes in gnomad4. There are 12 alleles in male gnomad4 subpopulation. Median coverage is 31. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High AC in GnomAd4 at 44 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBAP1	NM_016525.5 linkuse as main transcript	c.-104C>G		5_prime_UTR_variant	1/7	ENST00000297661.9	NP_057609.2	Q9NZ09-1A0A6G6AA68

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
UBAP1	ENST00000297661 linkuse as main transcript	c.-104C>G		5_prime_UTR_variant	1/7	1	NM_016525.5	ENSP00000297661.4	Q9NZ09-1
UBAP1	ENST00000625521.2 linkuse as main transcript	c.130C>G	p.Leu44Val	missense_variant	1/6	2		ENSP00000486574.1	Q9NZ09-4
UBAP1	ENST00000626262.2 linkuse as main transcript	c.100C>G	p.Leu34Val	missense_variant	1/6	2		ENSP00000487222.1	A0A0D9SG79
UBAP1	ENST00000379186 linkuse as main transcript	c.-104C>G		5_prime_UTR_variant	1/6	5		ENSP00000368484.3	Q9NZ09-2

Frequencies

GnomAD3 genomes

AF:

0.000289

AC:

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00101

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.000478

GnomAD4 exome

AF:

0.0000273

AC:

AN:

1099172

Hom.:

Cov.:

AF XY:

0.0000211

AC XY:

AN XY:

522548

show subpopulations

Gnomad4 AFR exome

AF:

0.00121

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:

0.0000451

GnomAD4 genome

AF:

0.000289

AC:

AN:

152234

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.00101

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Bravo

AF:

0.000370

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 01, 2024

The c.130C>G (p.L44V) 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 130, causing the leucine (L) at amino acid position 44 to be replaced by a valine (V). 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

-0.43

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0094

.;T

Eigen

Benign

-0.11

Eigen_PC

Benign

-0.12

FATHMM_MKL

Benign

0.10

LIST_S2

Benign

0.37

T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.24

T;T

MetaSVM

Benign

-0.95

PrimateAI

Uncertain

0.53

Sift4G

Pathogenic

0.0

D;D

Vest4

0.19

MVP

0.082

ClinPred

0.96

GERP RS

0.88

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

gMVP

0.057

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over