Variant 20-43513585-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001377303.1(L3MBTL1):c.82G>A(p.Gly28Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,550,616 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0015 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0022 ( 7 hom. )

Consequence

L3MBTL1
NM_001377303.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.38

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0066013336).

BP6

Variant 20-43513585-G-A is Benign according to our data. Variant chr20-43513585-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3048114.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
L3MBTL1	NM_001377303.1 linkuse as main transcript	c.82G>A	p.Gly28Arg	missense_variant	2/22	ENST00000418998.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
L3MBTL1	ENST00000418998.7 linkuse as main transcript	c.82G>A	p.Gly28Arg	missense_variant	2/22	2	NM_001377303.1

Frequencies

GnomAD3 genomes

AF:

0.00151

AC:

230

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00231

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00226

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00155

AC:

231

AN:

149476

Hom.:

AF XY:

0.00159

AC XY:

128

AN XY:

80462

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.00281

Gnomad ASJ exome

AF:

0.000954

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000311

Gnomad FIN exome

AF:

0.00101

Gnomad NFE exome

AF:

0.00198

Gnomad OTH exome

AF:

0.00300

GnomAD4 exome

AF:

0.00221

AC:

3089

AN:

1398354

Hom.:

Cov.:

AF XY:

0.00215

AC XY:

1484

AN XY:

689698

show subpopulations

Gnomad4 AFR exome

AF:

0.000506

Gnomad4 AMR exome

AF:

0.00274

Gnomad4 ASJ exome

AF:

0.00131

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000252

Gnomad4 FIN exome

AF:

0.00135

Gnomad4 NFE exome

AF:

0.00254

Gnomad4 OTH exome

AF:

0.00193

GnomAD4 genome

AF:

0.00151

AC:

230

AN:

152262

Hom.:

Cov.:

AF XY:

0.00160

AC XY:

119

AN XY:

74456

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00231

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00226

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00191

Hom.:

Bravo

AF:

0.00166

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00363

AC:

ExAC

AF:

0.000492

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

L3MBTL1-related disorder

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 22, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.70

Cadd

Benign

Dann

Benign

0.76

Eigen

Benign

-0.74

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.55

T;T;T

M_CAP

Benign

0.0079

MetaRNN

Benign

0.0066

T;T;T

MetaSVM

Benign

-1.1

MutationTaster

Benign

0.98

N;N

PrimateAI

Benign

0.45

REVEL

Benign

0.045

Vest4

0.077

MutPred

0.27

.;Gain of sheet (P = 0.0149);.;

MVP

0.061

MPC

0.21

ClinPred

0.014

GERP RS

4.8

Varity_R

0.035

gMVP

0.070

Splicing

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