Variant 14-70592883-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005466.4(MED6):c.463C>A(p.Gln155Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000186 in 1,613,456 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000018 ( 0 hom. )

Consequence

MED6
NM_005466.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.68

Variant links:

Genes affected

MED6 (HGNC:19970): (mediator complex subunit 6) Enables transcription coactivator activity. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of mediator complex. [provided by Alliance of Genome Resources, Apr 2022]

MED6 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0714702).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED6	NM_005466.4 link	c.463C>A	p.Gln155Lys	missense_variant	5/8	ENST00000256379.10	NP_005457.2	O75586-1
MED6	NM_001284211.2 link	c.463C>A	p.Gln155Lys	missense_variant	5/9		NP_001271140.1	O75586A0A087WYL7
MED6	NM_001284209.2 link	c.484C>A	p.Gln162Lys	missense_variant	5/8		NP_001271138.1	O75586-2
MED6	NM_001284210.2 link	c.463C>A	p.Gln155Lys	missense_variant	5/7		NP_001271139.1	O75586-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED6	ENST00000256379.10 link	c.463C>A	p.Gln155Lys	missense_variant	5/8	1	NM_005466.4	ENSP00000256379.5		O75586-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152132

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000239

AC:

AN:

251306

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135814

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000185

AC:

AN:

1461324

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

726974

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.000153

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000162

Gnomad4 OTH exome

AF:

0.0000662

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152132

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00000885

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000330

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

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

May 21, 2024

The c.463C>A (p.Q155K) alteration is located in exon 5 (coding exon 5) of the MED6 gene. This alteration results from a C to A substitution at nucleotide position 463, causing the glutamine (Q) at amino acid position 155 to be replaced by a lysine (K). 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

0.064

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.79

DEOGEN2

Benign

0.022

.;.;T;.;.

Eigen

Benign

-0.15

Eigen_PC

Benign

0.10

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.91

D;D;D;D;T

M_CAP

Benign

0.0020

MetaRNN

Benign

0.071

T;T;T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

-0.42

.;.;N;.;N

PrimateAI

Uncertain

0.56

PROVEAN

Benign

0.23

N;.;N;N;N

REVEL

Benign

0.062

Sift

Benign

0.87

T;.;T;T;T

Sift4G

Benign

0.96

T;T;T;T;T

Polyphen

0.0

B;.;B;.;.

Vest4

0.17

MutPred

0.33

Gain of methylation at Q155 (P = 0.0082);Gain of methylation at Q155 (P = 0.0082);Gain of methylation at Q155 (P = 0.0082);.;Gain of methylation at Q155 (P = 0.0082);

MVP

0.61

MPC

0.35

ClinPred

0.096

GERP RS

5.8

Varity_R

0.10

gMVP

0.44

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