Variant 20-43515312-C-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_001377303.1(L3MBTL1):c.674C>T(p.Ser225Phe) variant causes a missense change. The variant allele was found at a frequency of 0.00000438 in 1,599,984 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

L3MBTL1
NM_001377303.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.08

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 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	Protein	UniProt
L3MBTL1	NM_001377303.1 linkuse as main transcript	c.674C>T	p.Ser225Phe	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 linkuse as main transcript	c.674C>T	p.Ser225Phe	missense_variant	6/22	2	NM_001377303.1	ENSP00000398516.2		A0A3F2YNZ1
ENSG00000288000	ENST00000657241.1 linkuse as main transcript	c.1355C>T	p.Ser452Phe	missense_variant	10/26			ENSP00000499734.1		A0A590UK80

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000966

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

GnomAD3 exomes

AF:

0.00000447

AC:

AN:

223538

Hom.:

AF XY:

0.00

AC XY:

AN XY:

120758

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000316

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000207

AC:

AN:

1447866

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

719066

show subpopulations

Gnomad4 AFR exome

AF:

0.0000301

Gnomad4 AMR exome

AF:

0.0000470

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:

0.0000263

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.0000966

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

Alfa

AF:

0.0000658

Hom.:

Bravo

AF:

0.0000340

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 01, 2023

The c.608C>T (p.S203F) alteration is located in exon 6 (coding exon 5) of the L3MBTL1 gene. This alteration results from a C to T substitution at nucleotide position 608, causing the serine (S) at amino acid position 203 to be replaced by a phenylalanine (F). 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

0.16

BayesDel_addAF

Uncertain

0.12

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.036

.;.;.;.;.;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.79

LIST_S2

Uncertain

0.88

D;D;D;D;D;D

M_CAP

Uncertain

0.16

MetaRNN

Uncertain

0.61

D;D;D;D;D;D

MetaSVM

Uncertain

0.66

MutationAssessor

Uncertain

2.3

.;.;.;M;M;.

PrimateAI

Benign

0.47

PROVEAN

Benign

-2.2

.;N;.;.;N;N

REVEL

Uncertain

0.53

Sift

Uncertain

0.014

.;D;.;.;D;D

Sift4G

Benign

0.064

.;T;.;.;T;T

Polyphen

1.0

.;.;.;.;D;.

Vest4

0.34, 0.31, 0.36

MVP

0.92

MPC

0.72

ClinPred

0.85

GERP RS

2.8

Varity_R

0.21

gMVP

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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