chr9-34179067-G-T
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Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_016525.5(UBAP1):c.-181G>T variant causes a 5 prime UTR 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. 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_016525.5 5_prime_UTR
NM_016525.5 5_prime_UTR
Scores
1
2
10
Clinical Significance
Conservation
PhyloP100: 1.46
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -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 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 28 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
UBAP1 | NM_016525.5 | c.-181G>T | 5_prime_UTR_variant | 1/7 | ENST00000297661.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
UBAP1 | ENST00000297661.9 | c.-181G>T | 5_prime_UTR_variant | 1/7 | 1 | NM_016525.5 | P1 | ||
UBAP1 | ENST00000625521.2 | c.53G>T | p.Gly18Val | missense_variant | 1/6 | 2 | |||
UBAP1 | ENST00000626262.2 | c.23G>T | p.Gly8Val | missense_variant | 1/6 | 2 | |||
UBAP1 | ENST00000379186.8 | c.-181G>T | 5_prime_UTR_variant | 1/6 | 5 |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152150Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.000151 AC: 3AN: 19912Hom.: 0 AF XY: 0.000106 AC XY: 1AN XY: 9462
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GnomAD4 exome AF: 0.0000124 AC: 14AN: 1126936Hom.: 0 Cov.: 33 AF XY: 0.00000739 AC XY: 4AN XY: 540952
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GnomAD4 genome AF: 0.000184 AC: 28AN: 152268Hom.: 0 Cov.: 31 AF XY: 0.000228 AC XY: 17AN XY: 74448
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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 | Nov 14, 2023 | The c.53G>T (p.G18V) alteration is located in exon 1 (coding exon 1) of the UBAP1 gene. This alteration results from a G to T substitution at nucleotide position 53, causing the glycine (G) at amino acid position 18 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Pathogenic
D;D
Vest4
MVP
ClinPred
T
GERP RS
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at