Variant 19-16576266-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_004831.5(MED26):c.1564C>T(p.Arg522Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,611,184 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

MED26
NM_004831.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44

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 Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 12 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
MED26	NM_004831.5 linkuse as main transcript	c.1564C>T	p.Arg522Trp	missense_variant	3/3	ENST00000263390.8
LOC105372295	XR_936359.3 linkuse as main transcript	n.475-1900G>A		intron_variant, non_coding_transcript_variant
LOC105372295	XR_936360.3 linkuse as main transcript	n.260-1900G>A		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.1564C>T	p.Arg522Trp	missense_variant	3/3	1	NM_004831.5	P1	O95402-1
MED26	ENST00000611692.4 linkuse as main transcript	c.*929C>T		3_prime_UTR_variant	4/4	1			O95402-2
MED26	ENST00000597244.1 linkuse as main transcript	n.2512C>T		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0000789

AC:

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000290

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:

0.0000401

AC:

AN:

249514

Hom.:

AF XY:

0.0000148

AC XY:

AN XY:

135074

show subpopulations

Gnomad AFR exome

AF:

0.000616

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:

0.00000480

AC:

AN:

1459066

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

725952

show subpopulations

Gnomad4 AFR exome

AF:

0.000179

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000789

AC:

AN:

152118

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74312

show subpopulations

Gnomad4 AFR

AF:

0.000290

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

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000576

AC:

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

Jan 10, 2022

The c.1564C>T (p.R522W) alteration is located in exon 3 (coding exon 3) of the MED26 gene. This alteration results from a C to T substitution at nucleotide position 1564, causing the arginine (R) at amino acid position 522 to be replaced by a tryptophan (W). 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

0.12

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.26

Eigen

Benign

0.14

Eigen_PC

Benign

0.029

FATHMM_MKL

Benign

0.64

LIST_S2

Uncertain

0.93

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.47

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.42

PROVEAN

Uncertain

-3.4

REVEL

Benign

0.13

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.020

Polyphen

1.0

Vest4

0.64

MVP

0.18

MPC

0.99

ClinPred

0.28

GERP RS

1.2

Varity_R

0.17

gMVP

0.33

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