6-131596128-C-T

Position:

chr6-131596128-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_004830.4(MED23):c.2814G>A(p.Ala938Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,614,070 control chromosomes in the GnomAD database, including 12 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0017 ( 11 hom. )

Consequence

MED23
NM_004830.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -2.88

Variant links:

Genes affected

MED23 (HGNC:2372): (mediator complex subunit 23) The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. This protein also acts as a metastasis suppressor. Several alternatively spliced transcript variants encoding different isoforms have been described for this gene. [provided by RefSeq, Jul 2012]

MED23 links:

MED23 (HGNC:):

MED23 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.7).

BP6

Variant 6-131596128-C-T is Benign according to our data. Variant chr6-131596128-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 435852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.88 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00177 (269/152234) while in subpopulation SAS AF= 0.00249 (12/4824). AF 95% confidence interval is 0.00193. There are 1 homozygotes in gnomad4. There are 152 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED23	NM_004830.4 linkuse as main transcript	c.2814G>A	p.Ala938Ala	synonymous_variant	22/29	ENST00000368068.8	NP_004821.2	Q9ULK4-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED23	ENST00000368068.8 linkuse as main transcript	c.2814G>A	p.Ala938Ala	synonymous_variant	22/29	1	NM_004830.4	ENSP00000357047.3		Q9ULK4-1

Frequencies

GnomAD3 genomes

AF:

0.00177

AC:

269

AN:

152116

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00228

Gnomad FIN

AF:

0.00727

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00223

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00209

AC:

526

AN:

251270

Hom.:

AF XY:

0.00213

AC XY:

289

AN XY:

135796

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.000723

Gnomad ASJ exome

AF:

0.000198

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00291

Gnomad FIN exome

AF:

0.00651

Gnomad NFE exome

AF:

0.00220

Gnomad OTH exome

AF:

0.00212

GnomAD4 exome

AF:

0.00172

AC:

2510

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00182

AC XY:

1322

AN XY:

727216

show subpopulations

Gnomad4 AFR exome

AF:

0.000119

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.0000383

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00304

Gnomad4 FIN exome

AF:

0.00666

Gnomad4 NFE exome

AF:

0.00156

Gnomad4 OTH exome

AF:

0.00167

GnomAD4 genome

AF:

0.00177

AC:

269

AN:

152234

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

152

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.000289

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00249

Gnomad4 FIN

AF:

0.00727

Gnomad4 NFE

AF:

0.00222

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.000903

Asia WGS

AF:

0.000577

AC:

AN:

3478

EpiCase

AF:

0.00196

EpiControl

AF:

0.00178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Aug 01, 2024	MED23: BP4, BP7 -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Oct 29, 2015

- -

Inborn genetic diseases

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 06, 2016

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.70

CADD

Benign

0.17

DANN

Benign

0.27

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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