ENST00000361546.6:c.-42A>G

Variant names:

• chr1-154225082-A-G
• rs112188834
• ENST00000361546.6:c.-42A>G

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The ENST00000361546.6(UBAP2L):​c.-42A>G variant causes a 5 prime UTR change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBAP2L ENST00000361546.6 5_prime_UTR
• Scores: Splicing: ADA: 1.000
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.75
• Publications: 0 publications found

Genes affected

UBAP2L (HGNC:29877): (ubiquitin associated protein 2 like) Enables RNA binding activity. Involved in binding activity of sperm to zona pellucida and stress granule assembly. Acts upstream of or within hematopoietic stem cell homeostasis. Part of PcG protein complex. [provided by Alliance of Genome Resources, Apr 2022]

UBAP2L Gene-Disease associations (from GenCC):

• neurodevelopmental disorder with impaired language, behavioral abnormalities, and dysmorphic facies

  Inheritance: AD Classification: DEFINITIVE, MODERATE Submitted by: Ambry Genetics, G2P

ACMG classification

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: Splicing predictors support a deleterious effect. Scorers claiming Pathogenic: dbscSNV1_ADA, dbscSNV1_RF, max_spliceai. No scorers claiming Uncertain. No scorers claiming Benign.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361546.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAP2L	NM_014847.4	MANE Select	c.-40-2A>G		splice_acceptor intron	N/A	NP_055662.3
	UBAP2L	NM_001375612.1		c.-40-2A>G		splice_acceptor intron	N/A	NP_001362541.1
	UBAP2L	NM_001375614.1		c.-40-2A>G		splice_acceptor intron	N/A	NP_001362543.1	Q14157-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAP2L	ENST00000361546.6	TSL:1	c.-42A>G		5_prime_UTR	Exon 1 of 26	ENSP00000355343.2	Q14157-2
	UBAP2L	ENST00000428931.6	TSL:5 MANE Select	c.-40-2A>G		splice_acceptor intron	N/A	ENSP00000389445.1	Q14157-2
	UBAP2L	ENST00000343815.10	TSL:1	c.-40-2A>G		splice_acceptor intron	N/A	ENSP00000345308.6	Q14157-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000475 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	32
DANN	Benign	0.97
PhyloP100		6.8
PromoterAI		-0.015	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Pathogenic	1.0
dbscSNV1_RF	Pathogenic	0.95
SpliceAI score (max)		0.77		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.77		Position offset: 2

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

Other links and lift over

dbSNP: rs112188834; hg19: chr1-154197558;