15-65093152-A-C

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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

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.1091T>G	p.Val364Gly	missense_variant	Exon 6 of 6	ENST00000559089.6	NP_001157164.1
UBAP1L	XM_011521547.4	c.1279T>G	p.Ser427Ala	missense_variant	Exon 5 of 5		XP_011519849.1
UBAP1L	XM_017022172.3	c.*5914T>G		3_prime_UTR_variant	Exon 4 of 4		XP_016877661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAP1L	ENST00000559089.6	c.1091T>G	p.Val364Gly	missense_variant	Exon 6 of 6	1	NM_001163692.2	ENSP00000454012.1
UBAP1L	ENST00000561387.1	n.7234T>G		non_coding_transcript_exon_variant	Exon 2 of 2	1
UBAP1L	ENST00000558802.1	n.*156T>G		non_coding_transcript_exon_variant	Exon 4 of 4	5		ENSP00000452794.1
UBAP1L	ENST00000558802.1	n.*156T>G		3_prime_UTR_variant	Exon 4 of 4	5		ENSP00000452794.1

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

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000281

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 19, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1091T>G (p.V364G) alteration is located in exon 5 (coding exon 5) of the UBAP1L gene. This alteration results from a T to G substitution at nucleotide position 1091, causing the valine (V) at amino acid position 364 to be replaced by a glycine (G). 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	0.62
BayesDel_addAF	Pathogenic	0.17	D
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T;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;T
MetaSVM	Benign	-0.64	T
MutationAssessor	Benign	1.8	L;L
PrimateAI	Benign	0.39	T
PROVEAN	Pathogenic	-5.9	D;D
REVEL	Uncertain	0.35
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.32
MutPred		0.51		Loss of stability (P = 0.0037);Loss of stability (P = 0.0037);
MVP		0.16
ClinPred		0.99	D
GERP RS		4.2
Varity_R		0.58
gMVP		0.42

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: chr15-65385490;