15-65099598-C-A

Variant names:

• chr15-65099598-C-A
• rs2087216508
• NM_001163692.2:c.816G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001163692.2(UBAP1L):​c.816G>T​(p.Glu272Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,322 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.1e-7 (0 hom.)
• Consequence: UBAP1L NM_001163692.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

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 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP1L	NM_001163692.2	c.816G>T	p.Glu272Asp	missense_variant	Exon 4 of 6	ENST00000559089.6	NP_001157164.1
UBAP1L	XM_011521547.4	c.816G>T	p.Glu272Asp	missense_variant	Exon 3 of 5		XP_011519849.1
UBAP1L	XM_017022172.3	c.816G>T	p.Glu272Asp	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.816G>T	p.Glu272Asp	missense_variant	Exon 4 of 6	1	NM_001163692.2	ENSP00000454012.1
UBAP1L	ENST00000561387.1	n.2031G>T		non_coding_transcript_exon_variant	Exon 1 of 2	1
UBAP1L	ENST00000558802.1	n.240+2967G>T		intron_variant	Intron 2 of 3	5		ENSP00000452794.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1399322 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 690178

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.27e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 25, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.816G>T (p.E272D) alteration is located in exon 3 (coding exon 3) of the UBAP1L gene. This alteration results from a G to T substitution at nucleotide position 816, causing the glutamic acid (E) at amino acid position 272 to be replaced by an aspartic acid (D). 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	Pathogenic	0.93
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T;T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.80	.;T
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.61	D;D
MetaSVM	Benign	-0.53	T
MutationAssessor	Uncertain	2.1	M;M
PrimateAI	Uncertain	0.61	T
PROVEAN	Uncertain	-2.9	D;D
REVEL	Benign	0.27
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;D
Vest4		0.70
MutPred		0.44		Loss of helix (P = 0.0376);Loss of helix (P = 0.0376);
MVP		0.048
ClinPred		0.98	D
GERP RS		3.6
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.47
gMVP		0.56

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

Other links and lift over

dbSNP: rs2087216508; hg19: chr15-65391936;