Variant chr20-43515054-C-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_001377303.1(L3MBTL1):c.548C>T(p.Pro183Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,614,014 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00061 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 3 hom. )

Consequence

L3MBTL1
NM_001377303.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.557

Variant links:

Genes affected

L3MBTL1 (HGNC:15905): (L3MBTL histone methyl-lysine binding protein 1) This gene represents a polycomb group gene. The encoded protein functions to regulate gene activity, likely via chromatin modification. The encoded protein may also be necessary for mitosis. Alternatively spliced transcript variants encoding different isoforms have been identified.[provided by RefSeq, Sep 2010]

L3MBTL1 links:

ENSG00000288000 (HGNC:):

ENSG00000288000 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=0.028126895).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
L3MBTL1	NM_001377303.1 linkuse as main transcript	c.548C>T	p.Pro183Leu	missense_variant	5/22	ENST00000418998.7	NP_001364232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
L3MBTL1	ENST00000418998.7 linkuse as main transcript	c.548C>T	p.Pro183Leu	missense_variant	5/22	2	NM_001377303.1	ENSP00000398516.2		A0A3F2YNZ1
ENSG00000288000	ENST00000657241.1 linkuse as main transcript	c.1229C>T	p.Pro410Leu	missense_variant	9/26			ENSP00000499734.1		A0A590UK80

Frequencies

GnomAD3 genomes

AF:

0.000611

AC:

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.00125

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000541

AC:

136

AN:

251250

Hom.:

AF XY:

0.000464

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.00108

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.00110

AC:

1611

AN:

1461800

Hom.:

Cov.:

AF XY:

0.00106

AC XY:

774

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000243

Gnomad4 NFE exome

AF:

0.00132

Gnomad4 OTH exome

AF:

0.00207

GnomAD4 genome

AF:

0.000611

AC:

AN:

152214

Hom.:

Cov.:

AF XY:

0.000498

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.000145

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00125

Gnomad4 OTH

AF:

0.000478

Alfa

AF:

0.000804

Hom.:

Bravo

AF:

0.000654

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00104

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00151

AC:

ExAC

AF:

0.000618

AC:

EpiCase

AF:

0.00115

EpiControl

AF:

0.00142

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

Mar 25, 2024

The c.482C>T (p.P161L) alteration is located in exon 5 (coding exon 4) of the L3MBTL1 gene. This alteration results from a C to T substitution at nucleotide position 482, causing the proline (P) at amino acid position 161 to be replaced by a leucine (L). 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

-0.27

BayesDel_noAF

Benign

-0.21

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.032

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

Eigen

Benign

-0.43

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.030

LIST_S2

Benign

0.84

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

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.028

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

MetaSVM

Benign

-0.40

MutationAssessor

Uncertain

2.3

.;.;.;.;M;M;.

PrimateAI

Benign

0.36

PROVEAN

Pathogenic

-9.4

D;.;N;.;.;N;N

REVEL

Benign

0.25

Sift

Uncertain

0.0030

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

Sift4G

Pathogenic

0.0

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

Polyphen

0.0090

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

Vest4

0.31, 0.30, 0.34

MVP

0.67

MPC

0.27

ClinPred

0.082

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.041

gMVP

0.35

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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