Variant 6-130052957-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_032438.4(L3MBTL3):c.548C>A(p.Thr183Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.646 in 1,611,926 control chromosomes in the GnomAD database, including 346,134 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.54 ( 25359 hom., cov: 32)

Exomes 𝑓: 0.66 ( 320775 hom. )

Consequence

L3MBTL3
NM_032438.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.15

Variant links:

Genes affected

L3MBTL3 (HGNC:23035): (L3MBTL histone methyl-lysine binding protein 3) This gene encodes a member of the malignant brain tumor (MBT) family of chromatin interacting transcriptional repressors. Members of this family function as methyl-lysine readers, which recognize methylated lysine residues on histone protein tails, and are associated with the repression of gene expression. The encoded protein may regulate hematopoiesis. Homozygous deletion of this gene has been observed in human patients with medulloblastoma. [provided by RefSeq, Oct 2016]

L3MBTL3 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.322221E-6).

BP6

Variant 6-130052957-C-A is Benign according to our data. Variant chr6-130052957-C-A is described in ClinVar as [Benign]. Clinvar id is 1266479.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.742 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
L3MBTL3	NM_032438.4 linkuse as main transcript	c.548C>A	p.Thr183Asn	missense_variant	7/23	ENST00000361794.7	NP_115814.1	Q96JM7-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
L3MBTL3	ENST00000361794.7 linkuse as main transcript	c.548C>A	p.Thr183Asn	missense_variant	7/23	5	NM_032438.4	ENSP00000354526.2		Q96JM7-1

Frequencies

GnomAD3 genomes

AF:

0.537

AC:

81548

AN:

151840

Hom.:

25358

Cov.:

show subpopulations

Gnomad AFR

AF:

0.196

Gnomad AMI

AF:

0.570

Gnomad AMR

AF:

0.627

Gnomad ASJ

AF:

0.679

Gnomad EAS

AF:

0.761

Gnomad SAS

AF:

0.587

Gnomad FIN

AF:

0.661

Gnomad MID

AF:

0.620

Gnomad NFE

AF:

0.675

Gnomad OTH

AF:

0.576

GnomAD3 exomes

AF:

0.638

AC:

160163

AN:

250858

Hom.:

53251

AF XY:

0.644

AC XY:

87287

AN XY:

135630

show subpopulations

Gnomad AFR exome

AF:

0.190

Gnomad AMR exome

AF:

0.662

Gnomad ASJ exome

AF:

0.682

Gnomad EAS exome

AF:

0.769

Gnomad SAS exome

AF:

0.595

Gnomad FIN exome

AF:

0.669

Gnomad NFE exome

AF:

0.676

Gnomad OTH exome

AF:

0.653

GnomAD4 exome

AF:

0.658

AC:

959993

AN:

1459968

Hom.:

320775

Cov.:

AF XY:

0.657

AC XY:

477515

AN XY:

726340

show subpopulations

Gnomad4 AFR exome

AF:

0.179

Gnomad4 AMR exome

AF:

0.655

Gnomad4 ASJ exome

AF:

0.682

Gnomad4 EAS exome

AF:

0.722

Gnomad4 SAS exome

AF:

0.599

Gnomad4 FIN exome

AF:

0.670

Gnomad4 NFE exome

AF:

0.674

Gnomad4 OTH exome

AF:

0.645

GnomAD4 genome

AF:

0.537

AC:

81560

AN:

151958

Hom.:

25359

Cov.:

AF XY:

0.540

AC XY:

40106

AN XY:

74278

show subpopulations

Gnomad4 AFR

AF:

0.196

Gnomad4 AMR

AF:

0.626

Gnomad4 ASJ

AF:

0.679

Gnomad4 EAS

AF:

0.762

Gnomad4 SAS

AF:

0.587

Gnomad4 FIN

AF:

0.661

Gnomad4 NFE

AF:

0.675

Gnomad4 OTH

AF:

0.578

Alfa

AF:

0.649

Hom.:

70716

Bravo

AF:

0.523

TwinsUK

AF:

0.673

AC:

2496

ALSPAC

AF:

0.674

AC:

2596

ESP6500AA

AF:

0.212

AC:

934

ESP6500EA

AF:

0.681

AC:

5856

ExAC

AF:

0.626

AC:

76036

Asia WGS

AF:

0.644

AC:

2240

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 20, 2019

This variant is associated with the following publications: (PMID: 30389748) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.069

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.077

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

Eigen

Benign

-0.41

Eigen_PC

Benign

-0.23

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.16

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

MetaRNN

Benign

0.0000013

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

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

N;N;.;.;.;.;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.14

N;N;N;N;N;N;N

REVEL

Benign

0.033

Sift

Benign

0.10

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

Sift4G

Benign

0.34

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

Polyphen

0.0

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

Vest4

0.017

MPC

0.27

ClinPred

0.0066

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.065

gMVP

0.12

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