dbSNP rs1036048322: UBAP1L:p.Pro224Leu (chr15-65102134-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001163692.2(UBAP1L):c.671C>T(p.Pro224Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000555 in 1,206,386 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P224Q) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000054 ( 0 hom. )

Consequence

UBAP1L
NM_001163692.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.09

Variant links:

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]

UBAP1L links:

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ACMG classification

Classification made for transcript

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=0.19306323).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP1L	NM_001163692.2 link	c.671C>T	p.Pro224Leu	missense_variant	Exon 3 of 6	ENST00000559089.6	NP_001157164.1	F5GYI3
UBAP1L	XM_011521547.4 link	c.671C>T	p.Pro224Leu	missense_variant	Exon 2 of 5		XP_011519849.1
UBAP1L	XM_017022172.3 link	c.671C>T	p.Pro224Leu	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 link	c.671C>T	p.Pro224Leu	missense_variant	Exon 3 of 6	1	NM_001163692.2	ENSP00000454012.1		F5GYI3
UBAP1L	ENST00000558802.1 link	n.240+431C>T		intron_variant	Intron 2 of 3	5		ENSP00000452794.1		H0YKG2

Frequencies

GnomAD3 genomes

AF:

0.0000658

AC:

AN:

151990

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000541

AC:

AN:

1054396

Hom.:

Cov.:

AF XY:

0.0000683

AC XY:

AN XY:

498056

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.000380

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000565

Gnomad4 OTH exome

AF:

0.0000239

GnomAD4 genome

AF:

0.0000658

AC:

AN:

151990

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74252

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000869

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.083

BayesDel_noAF

Benign

-0.36

CADD

Benign

DANN

Benign

0.95

DEOGEN2

Benign

0.17

T;T

Eigen

Benign

-0.51

Eigen_PC

Benign

-0.56

FATHMM_MKL

Uncertain

0.93

LIST_S2

Benign

0.56

.;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.2

L;L

PrimateAI

Uncertain

0.68

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.22

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0080

D;D

Polyphen

0.98

D;D

Vest4

0.21

MutPred

0.20

Loss of catalytic residue at P223 (P = 0.0135);Loss of catalytic residue at P223 (P = 0.0135);

MVP

0.048

ClinPred

0.50

GERP RS

3.4

Varity_R

0.072

gMVP

0.41

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over