dbSNP rs1340872468: UBAP1L:p.Ser336Thr (chr15-65094479-C-G) – 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.1007G>C(p.Ser336Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBAP1L
NM_001163692.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.752

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:

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=0.11519185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP1L	NM_001163692.2 link	c.1007G>C	p.Ser336Thr	missense_variant	Exon 5 of 6	ENST00000559089.6	NP_001157164.1	F5GYI3
UBAP1L	XM_011521547.4 link	c.1007G>C	p.Ser336Thr	missense_variant	Exon 4 of 5		XP_011519849.1
UBAP1L	XM_017022172.3 link	c.*4587G>C		3_prime_UTR_variant	Exon 4 of 4		XP_016877661.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
UBAP1L	ENST00000559089.6 link	c.1007G>C	p.Ser336Thr	missense_variant	Exon 5 of 6	1	NM_001163692.2	ENSP00000454012.1	F5GYI3
UBAP1L	ENST00000561387.1 link	n.7150G>C		non_coding_transcript_exon_variant	Exon 1 of 2	1
UBAP1L	ENST00000558802.1 link	n.*72G>C		non_coding_transcript_exon_variant	Exon 3 of 4	5		ENSP00000452794.1	H0YKG2
UBAP1L	ENST00000558802.1 link	n.*72G>C		3_prime_UTR_variant	Exon 3 of 4	5		ENSP00000452794.1	H0YKG2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000132

AC:

AN:

151580

Hom.:

AF XY:

0.00

AC XY:

AN XY:

80460

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000184

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000215

AC:

AN:

1397474

Hom.:

Cov.:

AF XY:

0.00000290

AC XY:

AN XY:

689244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000560

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000173

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 08, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1007G>C (p.S336T) alteration is located in exon 4 (coding exon 4) of the UBAP1L gene. This alteration results from a G to C substitution at nucleotide position 1007, causing the serine (S) at amino acid position 336 to be replaced by a threonine (T). 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

-0.38

BayesDel_noAF

Benign

-0.50

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.021

T;T

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.11

FATHMM_MKL

Uncertain

0.76

LIST_S2

Benign

0.63

.;T

M_CAP

Benign

0.0051

MetaRNN

Benign

0.12

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.81

L;L

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.2

N;N

REVEL

Benign

0.058

Sift

Benign

0.29

T;T

Sift4G

Benign

0.49

T;T

Polyphen

0.87

P;P

Vest4

0.14

MutPred

0.22

Loss of disorder (P = 0.0488);Loss of disorder (P = 0.0488);

MVP

0.030

ClinPred

0.14

GERP RS

3.5

Varity_R

0.055

gMVP

0.14

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