Variant 19-16576053-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004831.5(MED26):c.1777A>G(p.Ile593Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0024 in 1,613,466 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0022 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0024 ( 8 hom. )

Consequence

MED26
NM_004831.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.96

Variant links:

Genes affected

MED26 (HGNC:2376): (mediator complex subunit 26) 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. [provided by RefSeq, Jul 2008]

MED26 links:

LOC105372295 (HGNC:):

LOC105372295 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0099549).

BP6

Variant 19-16576053-T-C is Benign according to our data. Variant chr19-16576053-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2649514.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 329 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MED26	NM_004831.5 linkuse as main transcript	c.1777A>G	p.Ile593Val	missense_variant	3/3	ENST00000263390.8
LOC105372295	XR_936359.3 linkuse as main transcript	n.475-2113T>C		intron_variant, non_coding_transcript_variant
LOC105372295	XR_936360.3 linkuse as main transcript	n.260-2113T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED26	ENST00000263390.8 linkuse as main transcript	c.1777A>G	p.Ile593Val	missense_variant	3/3	1	NM_004831.5	P1	O95402-1
MED26	ENST00000611692.4 linkuse as main transcript	c.*1142A>G		3_prime_UTR_variant	4/4	1			O95402-2
MED26	ENST00000597244.1 linkuse as main transcript	n.2725A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.00216

AC:

329

AN:

152058

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000556

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00585

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00321

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00200

AC:

502

AN:

250402

Hom.:

AF XY:

0.00189

AC XY:

256

AN XY:

135490

show subpopulations

Gnomad AFR exome

AF:

0.000432

Gnomad AMR exome

AF:

0.000492

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00463

Gnomad NFE exome

AF:

0.00328

Gnomad OTH exome

AF:

0.00131

GnomAD4 exome

AF:

0.00242

AC:

3543

AN:

1461292

Hom.:

Cov.:

AF XY:

0.00241

AC XY:

1750

AN XY:

726948

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00425

Gnomad4 NFE exome

AF:

0.00283

Gnomad4 OTH exome

AF:

0.00204

GnomAD4 genome

AF:

0.00216

AC:

329

AN:

152174

Hom.:

Cov.:

AF XY:

0.00226

AC XY:

168

AN XY:

74406

show subpopulations

Gnomad4 AFR

AF:

0.000554

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00585

Gnomad4 NFE

AF:

0.00321

Gnomad4 OTH

AF:

0.000947

Alfa

AF:

0.00274

Hom.:

Bravo

AF:

0.00184

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00244

AC:

ExAC

AF:

0.00190

AC:

231

EpiCase

AF:

0.00245

EpiControl

AF:

0.00273

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Feb 01, 2023

MED26: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.090

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.52

CADD

Benign

DANN

Benign

0.76

DEOGEN2

Benign

0.12

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.62

FATHMM_MKL

Uncertain

0.81

LIST_S2

Benign

0.78

M_CAP

Benign

0.0033

MetaRNN

Benign

0.010

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.1

MutationTaster

Benign

1.0

D;D

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.58

REVEL

Benign

0.027

Sift

Benign

0.20

Sift4G

Benign

0.18

Polyphen

0.0030

Vest4

0.13

MVP

0.26

MPC

0.26

ClinPred

0.0030

GERP RS

-0.34

Varity_R

0.037

gMVP

0.52

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