Variant 20-43515296-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001377303.1(L3MBTL1):c.658G>A(p.Val220Ile) variant causes a missense change. The variant allele was found at a frequency of 0.005 in 1,606,498 control chromosomes in the GnomAD database, including 25 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0035 ( 2 hom., cov: 33)

Exomes 𝑓: 0.0052 ( 23 hom. )

Consequence

L3MBTL1
NM_001377303.1 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 5.86

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 -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.010321081).

BP6

Variant 20-43515296-G-A is Benign according to our data. Variant chr20-43515296-G-A is described in ClinVar as [Benign]. Clinvar id is 716363.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
L3MBTL1	NM_001377303.1 link	c.658G>A	p.Val220Ile	missense_variant	6/22	ENST00000418998.7	NP_001364232.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
L3MBTL1	ENST00000418998.7 link	c.658G>A	p.Val220Ile	missense_variant	6/22	2	NM_001377303.1	ENSP00000398516.2		A0A3F2YNZ1
ENSG00000288000	ENST00000657241.1 link	c.1339G>A	p.Val447Ile	missense_variant	10/26			ENSP00000499734.1		A0A590UK80

Frequencies

GnomAD3 genomes

AF:

0.00350

AC:

533

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000772

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00372

Gnomad FIN

AF:

0.00697

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00536

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00401

AC:

940

AN:

234570

Hom.:

AF XY:

0.00421

AC XY:

534

AN XY:

126940

show subpopulations

Gnomad AFR exome

AF:

0.000953

Gnomad AMR exome

AF:

0.00198

Gnomad ASJ exome

AF:

0.000104

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00251

Gnomad FIN exome

AF:

0.00776

Gnomad NFE exome

AF:

0.00579

Gnomad OTH exome

AF:

0.00397

GnomAD4 exome

AF:

0.00516

AC:

7502

AN:

1454202

Hom.:

Cov.:

AF XY:

0.00503

AC XY:

3637

AN XY:

722816

show subpopulations

Gnomad4 AFR exome

AF:

0.000810

Gnomad4 AMR exome

AF:

0.00196

Gnomad4 ASJ exome

AF:

0.0000772

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00260

Gnomad4 FIN exome

AF:

0.00883

Gnomad4 NFE exome

AF:

0.00585

Gnomad4 OTH exome

AF:

0.00333

GnomAD4 genome

AF:

0.00350

AC:

533

AN:

152296

Hom.:

Cov.:

AF XY:

0.00340

AC XY:

253

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000770

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00697

Gnomad4 NFE

AF:

0.00536

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00485

Hom.:

Bravo

AF:

0.00292

TwinsUK

AF:

0.00458

AC:

ALSPAC

AF:

0.00623

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00535

AC:

ExAC

AF:

0.00373

AC:

452

Asia WGS

AF:

0.000577

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.099

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Uncertain

-0.060

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.025

.;.;.;.;.;T

Eigen

Uncertain

0.63

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.87

LIST_S2

Benign

0.83

T;T;T;T;T;T

MetaRNN

Benign

0.010

T;T;T;T;T;T

MetaSVM

Uncertain

0.74

MutationAssessor

Uncertain

2.5

.;.;.;M;M;.

PrimateAI

Uncertain

0.58

PROVEAN

Benign

-0.40

.;N;.;.;N;N

REVEL

Uncertain

0.53

Sift

Benign

0.18

.;T;.;.;D;D

Sift4G

Benign

0.17

.;T;.;.;T;T

Polyphen

1.0

.;.;.;.;D;.

Vest4

0.46, 0.48, 0.41

MVP

0.95

MPC

0.56

ClinPred

0.023

GERP RS

5.2

Varity_R

0.12

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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