chr15-65093152-A-C

Variant names:

• chr15-65093152-A-C
• rs2087137120
• NM_001163692.2:c.1091T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001163692.2(UBAP1L):​c.1091T>G​(p.Val364Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000716 in 1,396,842 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: UBAP1L NM_001163692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.07
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• inherited retinal dystrophy

  Inheritance: AR Classification: DEFINITIVE Submitted by: Ambry Genetics
• retinal degeneration

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001163692.2. 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
	UBAP1L	NM_001163692.2	MANE Select	c.1091T>G	p.Val364Gly	missense	Exon 6 of 6	NP_001157164.1	F5GYI3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	UBAP1L	ENST00000559089.6	TSL:1 MANE Select	c.1091T>G	p.Val364Gly	missense	Exon 6 of 6	ENSP00000454012.1	F5GYI3
	UBAP1L	ENST00000561387.1	TSL:1	n.7234T>G		non_coding_transcript_exon	Exon 2 of 2
	UBAP1L	ENST00000907325.1		c.1091T>G	p.Val364Gly	missense	Exon 5 of 5	ENSP00000577384.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1396842 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 689002

African (AFR) AF: 0.00 AC: 0 AN: 31506

American (AMR) AF: 0.00 AC: 0 AN: 35408

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25138

East Asian (EAS) AF: 0.0000281 AC: 1 AN: 35608

South Asian (SAS) AF: 0.00 AC: 0 AN: 79038

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48210

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5594

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078418

Other (OTH) AF: 0.00 AC: 0 AN: 57922

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.62
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.31
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.061	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.8	L
PhyloP100		7.1
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.9	D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D
Sift4G	Pathogenic	0.0010	D
Polyphen		1.0	D
Vest4		0.32
MutPred		0.51		Loss of stability (P = 0.0037)
MVP		0.16
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.58
gMVP		0.42
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs2087137120; hg19: chr15-65385490;