15-65099711-G-A

Variant names:

• chr15-65099711-G-A
• NM_001163692.2:c.703C>T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001163692.2(UBAP1L):​c.703C>T​(p.Leu235Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBAP1L NM_001163692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.41

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2791618).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP1L	NM_001163692.2	c.703C>T	p.Leu235Phe	missense_variant	Exon 4 of 6	ENST00000559089.6	NP_001157164.1
UBAP1L	XM_011521547.4	c.703C>T	p.Leu235Phe	missense_variant	Exon 3 of 5		XP_011519849.1
UBAP1L	XM_017022172.3	c.703C>T	p.Leu235Phe	missense_variant	Exon 3 of 4		XP_016877661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAP1L	ENST00000559089.6	c.703C>T	p.Leu235Phe	missense_variant	Exon 4 of 6	1	NM_001163692.2	ENSP00000454012.1
UBAP1L	ENST00000561387.1	n.1918C>T		non_coding_transcript_exon_variant	Exon 1 of 2	1
UBAP1L	ENST00000558802.1	n.240+2854C>T		intron_variant	Intron 2 of 3	5		ENSP00000452794.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 07, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.703C>T (p.L235F) alteration is located in exon 3 (coding exon 3) of the UBAP1L gene. This alteration results from a C to T substitution at nucleotide position 703, causing the leucine (L) at amino acid position 235 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.21
BayesDel_addAF	Uncertain	0.049	T
BayesDel_noAF	Benign	-0.17
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.057	T;T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.56
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.76	.;T
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.28	T;T
MetaSVM	Benign	-0.53	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.27
Sift	Benign	0.055	T;T
Sift4G	Benign	0.13	T;T
Polyphen		1.0	D;D
Vest4		0.32
MutPred		0.18		Loss of sheet (P = 0.0104);Loss of sheet (P = 0.0104);
MVP		0.092
ClinPred		0.99	D
GERP RS		5.2
Varity_R		0.37
gMVP		0.47

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-65392049;