Genetic Variant NM_001163692.2:c.710delC (chr15-65099703-CG-C) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate

The NM_001163692.2(UBAP1L):c.710delC(p.Pro237ArgfsTer32) variant causes a frameshift change. The variant allele was found at a frequency of 0.000011 in 1,549,080 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Pathogenic (★). Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

UBAP1L
NM_001163692.2 frameshift

Scores

Not classified

Clinical Significance

Pathogenic criteria provided, single submitter P:1

Conservation

PhyloP100: 4.00

Variant links:

Genes affected

UBAP1L (HGNC:40028): (ubiquitin associated protein 1 like) Predicted to enable ubiquitin binding activity. Predicted to be involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway. Predicted to be part of ESCRT I complex. [provided by Alliance of Genome Resources, Apr 2022]

UBAP1L links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP5

Variant 15-65099703-CG-C is Pathogenic according to our data. Variant chr15-65099703-CG-C is described in ClinVar as [Pathogenic]. Clinvar id is 3341499.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP1L	NM_001163692.2 link	c.710delC	p.Pro237ArgfsTer32	frameshift_variant	Exon 4 of 6	ENST00000559089.6	NP_001157164.1	F5GYI3
UBAP1L	XM_011521547.4 link	c.710delC	p.Pro237ArgfsTer32	frameshift_variant	Exon 3 of 5		XP_011519849.1
UBAP1L	XM_017022172.3 link	c.710delC	p.Pro237ArgfsTer32	frameshift_variant	Exon 3 of 4		XP_016877661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBAP1L	ENST00000559089.6 link	c.710delC	p.Pro237ArgfsTer32	frameshift_variant	Exon 4 of 6	1	NM_001163692.2	ENSP00000454012.1	F5GYI3
UBAP1L	ENST00000561387.1 link	n.1925delC		non_coding_transcript_exon_variant	Exon 1 of 2	1
UBAP1L	ENST00000558802.1 link	n.240+2861delC		intron_variant	Intron 2 of 3	5		ENSP00000452794.1	H0YKG2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000384

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000479

GnomAD4 exome

AF:

0.0000100

AC:

AN:

1396928

Hom.:

Cov.:

AF XY:

0.00000581

AC XY:

AN XY:

688668

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.000224

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000384

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000479

Bravo

AF:

0.0000378

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Retinal dystrophy

Pathogenic:1

Apr 15, 2024

NEI Ophthalmic Genomics Laboratory, National Institutes of Health

Significance: Pathogenic

Review Status: criteria provided, single submitter

Collection Method: research

The UBAP1L variant NM_001163692.2:c.710del was homozygous in three unrelated individuals with IRDs (PMIDs 39325468; 38420906). This variant is rare in gnomAD v4.1.0 (AF 0.00001097; PM2) and is predicted to result in frameshift and premature truncation (PVS1). In summary, the variant NM_001163692.2:c.710del is classified as Pathogenic following the ACMG/AMP guidelines (PMID 25741868). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over