rs796052212

Positions:

• chr1-202334984-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 5 ACMG points: 5P and 0B. PM2 PP3_Moderate PP5

The NM_014176.4(UBE2T):​c.179+5G>A variant causes a splice donor 5th base, intron 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. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBE2T NM_014176.4 splice_donor_5th_base, intron
• Scores: Splicing: ADA: 0.9998
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: 1.07

Genes affected

UBE2T (HGNC:25009): (ubiquitin conjugating enzyme E2 T) The protein encoded by this gene catalyzes the covalent attachment of ubiquitin to protein substrates. Defects in this gene have been associated with Fanconi anemia of complementation group T. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2015]

ACMG classification

Verdict is Uncertain_significance. Variant got 5 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing scoreres supports a deletorius effect: Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.
• PP5: Variant 1-202334984-C-T is Pathogenic according to our data. Variant chr1-202334984-C-T is described in ClinVar as [Pathogenic]. Clinvar id is 199437.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr1-202334984-C-T is described in Lovd as [Pathogenic].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBE2T	NM_014176.4	c.179+5G>A		splice_donor_5th_base_variant, intron_variant		ENST00000646651.1	NP_054895.1
UBE2T	NM_001310326.2	c.89+5G>A		splice_donor_5th_base_variant, intron_variant			NP_001297255.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBE2T	ENST00000646651.1	c.179+5G>A		splice_donor_5th_base_variant, intron_variant			NM_014176.4	ENSP00000494957	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Fanconi anemia complementation group T Pathogenic:2

Pathogenic, no assertion criteria provided	curation	Leiden Open Variation Database	Jul 19, 2015	Curator: Arleen D. Auerbach. Submitter to LOVD: Johan den Dunnen. -
Pathogenic, no assertion criteria provided	literature only	OMIM	Jun 04, 2015	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.21
CADD	Benign	17
DANN	Benign	0.92

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.96
SpliceAI score (max)		0.87		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.87		Position offset: 5

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs796052212; hg19: chr1-202304112;