9-34241294-T-C

Position:

• chr9-34241294-T-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_016525.5(UBAP1):​c.269T>C​(p.Val90Ala) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBAP1 NM_016525.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.69

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04855731).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBAP1	NM_016525.5	c.269T>C	p.Val90Ala	missense_variant	4/7	ENST00000297661.9	NP_057609.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBAP1	ENST00000297661.9	c.269T>C	p.Val90Ala	missense_variant	4/7	1	NM_016525.5	ENSP00000297661.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 30, 2023

The c.461T>C (p.V154A) alteration is located in exon 3 (coding exon 3) of the UBAP1 gene. This alteration results from a T to C substitution at nucleotide position 461, causing the valine (V) at amino acid position 154 to be replaced by an alanine (A). 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
AlphaMissense	Benign	0.10
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.064	.;T;.;T;T
Eigen	Benign	-0.53
Eigen_PC	Benign	-0.33
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.58	T;.;T;T;T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.049	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	.;L;L;.;L
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-0.11	.;N;N;.;N
REVEL	Benign	0.041
Sift	Benign	0.66	.;T;T;.;T
Sift4G	Benign	0.72	T;T;T;T;T
Polyphen		0.0	.;B;.;.;B
Vest4		0.058
MutPred		0.11		.;Gain of relative solvent accessibility (P = 0.0166);Gain of relative solvent accessibility (P = 0.0166);.;Gain of relative solvent accessibility (P = 0.0166);
MVP		0.17
ClinPred		0.078	T
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.016
gMVP		0.25

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.

Other links and lift over

hg19: chr9-34241292;