Genetic Variant UBAP1L:p.Thr218Ala (chr15-65102153-T-C) – 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.652A>G(p.Thr218Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000456 in 1,202,710 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 0 hom. )

Consequence

UBAP1L
NM_001163692.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.420

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=0.07405171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP1L	NM_001163692.2 link	c.652A>G	p.Thr218Ala	missense_variant	Exon 3 of 6	ENST00000559089.6	NP_001157164.1	F5GYI3
UBAP1L	XM_011521547.4 link	c.652A>G	p.Thr218Ala	missense_variant	Exon 2 of 5		XP_011519849.1
UBAP1L	XM_017022172.3 link	c.652A>G	p.Thr218Ala	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.652A>G	p.Thr218Ala	missense_variant	Exon 3 of 6	1	NM_001163692.2	ENSP00000454012.1		F5GYI3
UBAP1L	ENST00000558802.1 link	n.240+412A>G		intron_variant	Intron 2 of 3	5		ENSP00000452794.1		H0YKG2

Frequencies

GnomAD3 genomes

AF:

0.000595

AC:

AN:

149568

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00131

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00110

Gnomad OTH

AF:

0.000974

GnomAD4 exome

AF:

0.000436

AC:

459

AN:

1053044

Hom.:

Cov.:

AF XY:

0.000440

AC XY:

219

AN XY:

497442

show subpopulations

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:

0.00198

Gnomad4 NFE exome

AF:

0.000451

Gnomad4 OTH exome

AF:

0.000265

GnomAD4 genome

AF:

0.000595

AC:

AN:

149666

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

73032

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00131

Gnomad4 NFE

AF:

0.00110

Gnomad4 OTH

AF:

0.000963

Alfa

AF:

0.00127

Hom.:

Bravo

AF:

0.000393

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Oct 06, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.652A>G (p.T218A) alteration is located in exon 2 (coding exon 2) of the UBAP1L gene. This alteration results from a A to G substitution at nucleotide position 652, causing the threonine (T) at amino acid position 218 to be replaced by an alanine (A). 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

Benign

0.22

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.55

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.015

T;T

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.51

FATHMM_MKL

Benign

0.64

LIST_S2

Benign

0.43

.;T

M_CAP

Benign

0.0097

MetaRNN

Benign

0.074

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.1

L;L

PrimateAI

Uncertain

0.79

PROVEAN

Benign

-1.3

N;N

REVEL

Benign

0.010

Sift

Benign

0.14

T;T

Sift4G

Benign

0.099

T;T

Polyphen

0.30

B;B

Vest4

0.074

MVP

0.014

ClinPred

0.37

GERP RS

1.8

Varity_R

0.094

gMVP

0.47

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over