Variant 3-151086958-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate

The NM_001393769.1(MED12L):c.32A>G(p.Gln11Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000275 in 1,457,100 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: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

MED12L
NM_001393769.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.06

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

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=0.124240965).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED12L	NM_001393769.1 linkuse as main transcript	c.32A>G	p.Gln11Arg	missense_variant	2/45	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.32A>G	p.Gln11Arg	missense_variant	2/45		NM_001393769.1	ENSP00000508695	A2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000424

AC:

AN:

236114

Hom.:

AF XY:

0.00000772

AC XY:

AN XY:

129492

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.00000946

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000275

AC:

AN:

1457100

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

724584

show subpopulations

Gnomad4 AFR exome

AF:

0.00

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:

0.00000360

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 07, 2023

The c.32A>G (p.Q11R) alteration is located in exon 1 (coding exon 1) of the MED12L gene. This alteration results from a A to G substitution at nucleotide position 32, causing the glutamine (Q) at amino acid position 11 to be replaced by an arginine (R). 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

0.28

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.010

.;.;T;.

Eigen

Benign

0.078

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.83

T;T;T;T

M_CAP

Uncertain

0.13

MetaRNN

Benign

0.12

T;T;T;T

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.14

N;N;N;.

MutationTaster

Benign

0.96

D;D;D;N

PrimateAI

Pathogenic

0.79

PROVEAN

Benign

-0.13

N;N;N;N

REVEL

Benign

0.16

Sift

Benign

0.24

T;T;T;T

Sift4G

Benign

0.51

T;T;T;T

Polyphen

0.40

B;B;P;B

Vest4

0.19

MutPred

0.21

Gain of glycosylation at Y9 (P = 0.0017);Gain of glycosylation at Y9 (P = 0.0017);Gain of glycosylation at Y9 (P = 0.0017);Gain of glycosylation at Y9 (P = 0.0017);

MVP

0.068

MPC

1.1

ClinPred

0.58

GERP RS

4.6

Varity_R

0.37

gMVP

0.50

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