Genetic Variant UBAP2L:p.Ser145Asn (chr1-154234745-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_014847.4(UBAP2L):c.434G>A(p.Ser145Asn) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (no stars).

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

UBAP2L
NM_014847.4 missense

Scores

Clinical Significance

Uncertain significance no assertion criteria provided U:1

Conservation

PhyloP100: 6.44

Variant links:

Genes affected

UBAP2L (HGNC:29877): (ubiquitin associated protein 2 like) Enables RNA binding activity. Involved in binding activity of sperm to zona pellucida and stress granule assembly. Acts upstream of or within hematopoietic stem cell homeostasis. Part of PcG protein complex. [provided by Alliance of Genome Resources, Apr 2022]

UBAP2L 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=0.19366294).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
UBAP2L	NM_014847.4 link	c.434G>A	p.Ser145Asn	missense_variant	Exon 5 of 27	ENST00000428931.6	NP_055662.3	Q14157-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
UBAP2L	ENST00000428931.6 link	c.434G>A	p.Ser145Asn	missense_variant	Exon 5 of 27	5	NM_014847.4	ENSP00000389445.1		Q14157-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1447384

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

718512

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:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

UBAP2L-related condition

Uncertain:1

Sep 05, 2024

PreventionGenetics, part of Exact Sciences

Significance: Uncertain significance

Review Status: no assertion criteria provided

Collection Method: clinical testing

The UBAP2L c.434G>A variant is predicted to result in the amino acid substitution p.Ser145Asn. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.29

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.51

CADD

Pathogenic

DANN

Benign

0.90

DEOGEN2

Benign

0.14

.;T;T;T;T;T;T;T

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.60

T;T;D;D;D;D;D;.

M_CAP

Benign

0.0070

MetaRNN

Benign

0.19

T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.3

L;L;.;.;.;.;.;L

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-1.0

N;N;N;N;N;N;N;N

REVEL

Benign

0.084

Sift

Benign

0.53

T;T;T;T;T;T;T;T

Sift4G

Benign

0.25

T;T;T;T;T;T;T;T

Polyphen

0.45

B;B;B;.;.;.;.;B

Vest4

0.34

MutPred

0.30

Loss of phosphorylation at S145 (P = 5e-04);Loss of phosphorylation at S145 (P = 5e-04);Loss of phosphorylation at S145 (P = 5e-04);Loss of phosphorylation at S145 (P = 5e-04);Loss of phosphorylation at S145 (P = 5e-04);Loss of phosphorylation at S145 (P = 5e-04);Loss of phosphorylation at S145 (P = 5e-04);Loss of phosphorylation at S145 (P = 5e-04);

MVP

0.27

MPC

0.63

ClinPred

0.54

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.17

gMVP

0.52

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over