Variant 1-154251064-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_014847.4(UBAP2L):c.1237G>T(p.Ala413Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000509 in 1,612,062 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

UBAP2L
NM_014847.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0490

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02386871).

BS2

High AC in GnomAd4 at 11 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
UBAP2L	NM_014847.4 linkuse as main transcript	c.1237G>T	p.Ala413Ser	missense_variant	13/27	ENST00000428931.6	NP_055662.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
UBAP2L	ENST00000428931.6 linkuse as main transcript	c.1237G>T	p.Ala413Ser	missense_variant	13/27	5	NM_014847.4	ENSP00000389445	A1	Q14157-2

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152112

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

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:

0.0000735

Gnomad OTH

AF:

0.000960

GnomAD3 exomes

AF:

0.0000319

AC:

AN:

250548

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

135396

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000290

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:

0.0000618

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000486

AC:

AN:

1459950

Hom.:

Cov.:

AF XY:

0.0000427

AC XY:

AN XY:

725922

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000896

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000188

Gnomad4 NFE exome

AF:

0.0000513

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000723

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.0000942

AC XY:

AN XY:

74314

show subpopulations

Gnomad4 AFR

AF:

0.0000483

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000735

Gnomad4 OTH

AF:

0.000960

Alfa

AF:

0.000131

Hom.:

Bravo

AF:

0.0000945

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.0000247

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 23, 2024

The c.1237G>T (p.A413S) alteration is located in exon 13 (coding exon 12) of the UBAP2L gene. This alteration results from a G to T substitution at nucleotide position 1237, causing the alanine (A) at amino acid position 413 to be replaced by a serine (S). 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

0.067

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.79

CADD

Benign

1.6

DANN

Benign

0.85

DEOGEN2

Benign

0.080

.;.;T;T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.077

LIST_S2

Benign

0.79

T;T;T;T;.

M_CAP

Benign

0.0082

MetaRNN

Benign

0.024

T;T;T;T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

-1.0

N;.;N;.;N

MutationTaster

Benign

1.0

N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-0.28

N;.;N;N;N

REVEL

Benign

0.032

Sift

Benign

0.13

T;.;T;T;T

Sift4G

Benign

1.0

T;T;T;T;T

Polyphen

0.0

B;B;B;B;B

Vest4

0.076

MVP

0.23

MPC

0.62

ClinPred

0.025

GERP RS

-4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.036

gMVP

0.18

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