Variant 3-151122966-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4BS2

The NM_001393769.1(MED12L):c.388G>T(p.Ala130Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000752 in 1,595,832 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000042 ( 0 hom. )

Consequence

MED12L
NM_001393769.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.79

Variant links:

Genes affected

MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

MED12L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PP2

Missense variant in gene, where missense usually causes diseases (based on misZ statistic), MED12L. . Gene score misZ 3.132 (greater than the threshold 3.09). Trascript score misZ 3.991 (greater than threshold 3.09). GenCC has associacion of gene with Nizon-Isidor syndrome, autosomal dominant non-syndromic intellectual disability.

BP4

Computational evidence support a benign effect (MetaRNN=0.32478198).

BS2

High AC in GnomAd4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED12L	NM_001393769.1 linkuse as main transcript	c.388G>T	p.Ala130Ser	missense_variant	4/45	ENST00000687756.1	NP_001380698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED12L	ENST00000687756.1 linkuse as main transcript	c.388G>T	p.Ala130Ser	missense_variant	4/45		NM_001393769.1	ENSP00000508695	A2

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151960

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

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:

0.0000127

AC:

AN:

235874

Hom.:

AF XY:

0.0000157

AC XY:

AN XY:

127434

show subpopulations

Gnomad AFR exome

AF:

0.000196

Gnomad AMR exome

AF:

0.00

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:

0.00000416

AC:

AN:

1443872

Hom.:

Cov.:

AF XY:

0.00000279

AC XY:

AN XY:

717630

show subpopulations

Gnomad4 AFR exome

AF:

0.000155

Gnomad4 AMR exome

AF:

0.00

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:

9.05e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151960

Hom.:

Cov.:

AF XY:

0.0000539

AC XY:

AN XY:

74214

show subpopulations

Gnomad4 AFR

AF:

0.000145

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:

0.0000712

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 03, 2024

The c.388G>T (p.A130S) alteration is located in exon 3 (coding exon 3) of the MED12L gene. This alteration results from a G to T substitution at nucleotide position 388, causing the alanine (A) at amino acid position 130 to be replaced by a serine (S). 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

Benign

-0.16

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.031

.;.;T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.030

MetaRNN

Benign

0.32

T;T;T;T

MetaSVM

Benign

-0.54

MutationAssessor

Benign

0.95

L;L;L;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-1.2

N;N;N;N

REVEL

Benign

0.22

Sift

Benign

0.16

T;T;T;D

Sift4G

Benign

0.19

T;T;T;T

Polyphen

0.96

D;D;D;D

Vest4

0.58

MVP

0.082

MPC

0.62

ClinPred

0.45

GERP RS

5.4

Varity_R

0.22

gMVP

0.41

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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