15-65102134-G-T

Variant names:

• chr15-65102134-G-T
• rs1036048322
• NM_001163692.2:c.671C>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Moderate BP6_Moderate

The NM_001163692.2(UBAP1L):​c.671C>A​(p.Pro224Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000285 in 1,054,394 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000028 (0 hom.)
• Consequence: UBAP1L NM_001163692.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.09

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.09458792).
• BP6: Variant 15-65102134-G-T is Benign according to our data. Variant chr15-65102134-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2280561.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP1L	NM_001163692.2	c.671C>A	p.Pro224Gln	missense_variant	Exon 3 of 6	ENST00000559089.6	NP_001157164.1
UBAP1L	XM_011521547.4	c.671C>A	p.Pro224Gln	missense_variant	Exon 2 of 5		XP_011519849.1
UBAP1L	XM_017022172.3	c.671C>A	p.Pro224Gln	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.671C>A	p.Pro224Gln	missense_variant	Exon 3 of 6	1	NM_001163692.2	ENSP00000454012.1
UBAP1L	ENST00000558802.1	n.240+431C>A		intron_variant	Intron 2 of 3	5		ENSP00000452794.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000285 AC: 3 AN: 1054394 Hom.: 0 Cov.: 27 AF XY: 0.00000402 AC XY: 2 AN XY: 498056

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: 0.0000517

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000222

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2022

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	20
DANN	Benign	0.77
DEOGEN2	Benign	0.097	T;T
Eigen	Benign	-0.91
Eigen_PC	Benign	-0.84
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.43	.;T
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.095	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L;L
PrimateAI	Uncertain	0.64	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.067
Sift	Benign	0.083	T;T
Sift4G	Benign	0.062	T;T
Polyphen		0.18	B;B
Vest4		0.16
MutPred		0.22		Loss of catalytic residue at P223 (P = 0.0096);Loss of catalytic residue at P223 (P = 0.0096);
MVP		0.014
ClinPred		0.14	T
GERP RS		3.4
Varity_R		0.040
gMVP		0.43

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: rs1036048322; hg19: chr15-65394472;