15-65093180-G-T

Variant summary

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

The NM_001163692.2(UBAP1L):​c.1063C>A​(p.Gln355Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000839 in 1,549,962 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)
Exomes 𝑓: 0.0000079 ( 1 hom. )

Consequence

UBAP1L
NM_001163692.2 missense

Scores

1
3
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.70
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]

Genome browser will be placed here

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=0.1782572).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
UBAP1LNM_001163692.2 linkc.1063C>A p.Gln355Lys missense_variant Exon 6 of 6 ENST00000559089.6 NP_001157164.1 F5GYI3
UBAP1LXM_011521547.4 linkc.1251C>A p.Ser417Arg missense_variant Exon 5 of 5 XP_011519849.1
UBAP1LXM_017022172.3 linkc.*5886C>A 3_prime_UTR_variant Exon 4 of 4 XP_016877661.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
UBAP1LENST00000559089.6 linkc.1063C>A p.Gln355Lys missense_variant Exon 6 of 6 1 NM_001163692.2 ENSP00000454012.1 F5GYI3
UBAP1LENST00000561387.1 linkn.7206C>A non_coding_transcript_exon_variant Exon 2 of 2 1
UBAP1LENST00000558802.1 linkn.*128C>A non_coding_transcript_exon_variant Exon 4 of 4 5 ENSP00000452794.1 H0YKG2
UBAP1LENST00000558802.1 linkn.*128C>A 3_prime_UTR_variant Exon 4 of 4 5 ENSP00000452794.1 H0YKG2

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152156
Hom.:
0
Cov.:
33
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000262
AC:
4
AN:
152592
Hom.:
0
AF XY:
0.0000123
AC XY:
1
AN XY:
81168
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000123
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000169
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000787
AC:
11
AN:
1397806
Hom.:
1
Cov.:
30
AF XY:
0.00000435
AC XY:
3
AN XY:
689452
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000845
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000556
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152156
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74332
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:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000283
Hom.:
0
Bravo
AF:
0.0000227

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Aug 09, 2021
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.1063C>A (p.Q355K) alteration is located in exon 5 (coding exon 5) of the UBAP1L gene. This alteration results from a C to A substitution at nucleotide position 1063, causing the glutamine (Q) at amino acid position 355 to be replaced by a lysine (K). 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
0.10
BayesDel_addAF
Benign
-0.25
T
BayesDel_noAF
Benign
-0.36
CADD
Benign
23
DANN
Benign
0.87
DEOGEN2
Benign
0.037
T;T
Eigen
Uncertain
0.26
Eigen_PC
Uncertain
0.31
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.76
.;T
M_CAP
Benign
0.022
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-0.75
T
MutationAssessor
Benign
1.8
L;L
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-1.6
N;N
REVEL
Benign
0.19
Sift
Benign
0.17
T;T
Sift4G
Benign
0.12
T;T
Polyphen
0.78
P;P
Vest4
0.17
MutPred
0.29
Gain of ubiquitination at Q355 (P = 0.017);Gain of ubiquitination at Q355 (P = 0.017);
MVP
0.081
ClinPred
0.25
T
GERP RS
5.2
Varity_R
0.34
gMVP
0.32

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.040
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.

Other links and lift over

dbSNP: rs965536840; hg19: chr15-65385518; API