Variant 20-45311637-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014276.4(RBPJL):c.306G>T(p.Arg102Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,614,084 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

RBPJL
NM_014276.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.761

Variant links:

Genes affected

RBPJL (HGNC:13761): (recombination signal binding protein for immunoglobulin kappa J region like) This gene encodes a member of the suppressor of hairless protein family. A similar protein in mouse is a transcription factor that binds to DNA sequences almost identical to that bound by the Notch receptor signaling pathway transcription factor recombining binding protein J. The mouse protein has been shown to activate transcription in concert with Epstein-Barr virus nuclear antigen-2. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2013]

RBPJL links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
RBPJL	NM_014276.4 linkuse as main transcript	c.306G>T	p.Arg102Ser	missense_variant	4/12	ENST00000343694.8
RBPJL	NM_001281449.2 linkuse as main transcript	c.306G>T	p.Arg102Ser	missense_variant	4/12
RBPJL	NM_001281448.2 linkuse as main transcript	c.306G>T	p.Arg102Ser	missense_variant	4/12
RBPJL	XM_011528522.3 linkuse as main transcript	c.306G>T	p.Arg102Ser	missense_variant	4/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RBPJL	ENST00000343694.8 linkuse as main transcript	c.306G>T	p.Arg102Ser	missense_variant	4/12	1	NM_014276.4	A1	Q9UBG7-1
RBPJL	ENST00000372743.5 linkuse as main transcript	c.306G>T	p.Arg102Ser	missense_variant	4/12	1		P4	Q9UBG7-2
RBPJL	ENST00000372741.7 linkuse as main transcript	c.306G>T	p.Arg102Ser	missense_variant	4/12	1

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000482

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

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

AF:

0.0000131

AC:

AN:

152220

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74374

show subpopulations

Gnomad4 AFR

AF:

0.0000482

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:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

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

Aug 22, 2022

The c.306G>T (p.R102S) alteration is located in exon 4 (coding exon 4) of the RBPJL gene. This alteration results from a G to T substitution at nucleotide position 306, causing the arginine (R) at amino acid position 102 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

0.20

BayesDel_addAF

Uncertain

0.053

BayesDel_noAF

Benign

-0.16

Cadd

Benign

Dann

Uncertain

0.99

Eigen

Uncertain

0.25

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.75

T;T;T

M_CAP

Benign

0.068

MetaRNN

Uncertain

0.49

T;T;T

MetaSVM

Uncertain

-0.15

MutationAssessor

Benign

1.4

L;.;L

MutationTaster

Benign

0.96

D;D;D

PrimateAI

Uncertain

0.53

PROVEAN

Benign

-1.7

N;N;N

REVEL

Uncertain

0.43

Sift

Uncertain

0.012

D;D;D

Sift4G

Uncertain

0.052

T;T;T

Polyphen

0.93

.;P;P

Vest4

0.34

MutPred

0.60

Loss of catalytic residue at R102 (P = 0.0437);Loss of catalytic residue at R102 (P = 0.0437);Loss of catalytic residue at R102 (P = 0.0437);

MVP

0.83

MPC

0.71

ClinPred

0.73

GERP RS

5.1

Varity_R

0.24

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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