15-65102153-T-G

Variant names:

• chr15-65102153-T-G
• rs923123336
• NM_001163692.2:c.652A>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001163692.2(UBAP1L):​c.652A>C​(p.Thr218Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: UBAP1L NM_001163692.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.19389588).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP1L	NM_001163692.2	c.652A>C	p.Thr218Pro	missense_variant	Exon 3 of 6	ENST00000559089.6	NP_001157164.1
UBAP1L	XM_011521547.4	c.652A>C	p.Thr218Pro	missense_variant	Exon 2 of 5		XP_011519849.1
UBAP1L	XM_017022172.3	c.652A>C	p.Thr218Pro	missense_variant	Exon 2 of 4		XP_016877661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAP1L	ENST00000559089.6	c.652A>C	p.Thr218Pro	missense_variant	Exon 3 of 6	1	NM_001163692.2	ENSP00000454012.1
UBAP1L	ENST00000558802.1	n.240+412A>C		intron_variant	Intron 2 of 3	5		ENSP00000452794.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	21
DANN	Uncertain	0.98
DEOGEN2	Benign	0.017	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.20
FATHMM_MKL	Benign	0.48	N
LIST_S2	Benign	0.44	.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.19	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;L
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.4	N;N
REVEL	Benign	0.21
Sift	Benign	0.17	T;T
Sift4G	Uncertain	0.048	D;D
Polyphen		0.97	D;D
Vest4		0.098
MutPred		0.067		Loss of phosphorylation at T218 (P = 0.0044);Loss of phosphorylation at T218 (P = 0.0044);
MVP		0.030
ClinPred		0.65	D
GERP RS		1.8
Varity_R		0.25
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs923123336; hg19: chr15-65394491;