13-38349922-G-A

Position:

• chr13-38349922-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP5

The ENST00000239878.9(UFM1):​c.2+1G>A variant causes a splice donor change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Likely pathogenic (no stars).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UFM1 ENST00000239878.9 splice_donor
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Likely pathogenic no assertion criteria provided P:1
• Conservation: PhyloP100: 5.02

Genes affected

UFM1 (HGNC:20597): (ubiquitin fold modifier 1) UFM1 is a ubiquitin-like protein that is conjugated to target proteins by E1-like activating enzyme UBA5 (UBE1DC1; MIM 610552) and E2-like conjugating enzyme UFC1 (MIM 610554) in a manner analogous to ubiquitylation (see UBE2M; MIM 603173) (Komatsu et al., 2004 [PubMed 15071506]).[supplied by OMIM, Dec 2008]

LINC00571 (HGNC:43721): (long intergenic non-protein coding RNA 571)

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 13-38349922-G-A is Pathogenic according to our data. Variant chr13-38349922-G-A is described in ClinVar as [Likely_pathogenic]. Clinvar id is 3358901.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UFM1	NM_016617.4	c.2+1G>A		splice_donor_variant		ENST00000239878.9	NP_057701.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UFM1	ENST00000239878.9	c.2+1G>A		splice_donor_variant		1	NM_016617.4	ENSP00000239878	P1
LINC00571	ENST00000454060.2	n.322+16C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely pathogenic

Submissions summary: Pathogenic:1

Revision: no assertion criteria provided

Submissions by phenotype

Congenital long QT syndrome Pathogenic:1

Likely pathogenic, no assertion criteria provided

research

Genetics and Genomics Program, Sidra Medicine

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The c.-117+1G>A splice donor variant in UFM1 is a null variant (intronic, within ±2 of the splice site), likely leading to loss of function (PVS1). The variant is absent from gnomAD supporting its rarity (PM2). The evidence supports a likely pathogenic classification (ACMG codes: PVS1, PM2). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.24	D
BayesDel_noAF	Uncertain	0.10
CADD	Pathogenic	28
DANN	Uncertain	0.99
Eigen	Pathogenic	0.95
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Uncertain	0.93	D
MutationTaster	Benign	1.0	D;D
GERP RS		5.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.8

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.86
SpliceAI score (max)		0.94		Details are displayed if max score is > 0.2
DS_DL_spliceai		0.94		Position offset: -1

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: chr13-38924059;