Variant 19-49818601-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_030973.4(MED25):c.165G>A(p.Thr55Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,614,030 control chromosomes in the GnomAD database, including 1,331 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.022 ( 83 hom., cov: 33)

Exomes 𝑓: 0.029 ( 1248 hom. )

Consequence

MED25
NM_030973.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.285

Variant links:

Genes affected

MED25 (HGNC:28845): (mediator complex subunit 25) This gene encodes a component of the transcriptional coactivator complex termed the Mediator complex. This complex is required for transcription of most RNA polymerase II-dependent genes. The encoded protein plays a role in chromatin modification and in preinitiation complex assembly. Mutations in this gene are associated with Charcot-Marie-Tooth disease type 2B2. [provided by RefSeq, Apr 2010]

MED25 links:

MED25 (HGNC:):

MED25 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 19-49818601-G-A is Benign according to our data. Variant chr19-49818601-G-A is described in ClinVar as [Benign]. Clinvar id is 195384.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-49818601-G-A is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.285 with no splicing effect.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED25	NM_030973.4 linkuse as main transcript	c.165G>A	p.Thr55Thr	synonymous_variant	2/18	ENST00000312865.10	NP_112235.2	Q71SY5-1
MED25	NM_001378355.1 linkuse as main transcript	c.165G>A	p.Thr55Thr	synonymous_variant	2/18		NP_001365284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED25	ENST00000312865.10 linkuse as main transcript	c.165G>A	p.Thr55Thr	synonymous_variant	2/18	1	NM_030973.4	ENSP00000326767.5		Q71SY5-1

Frequencies

GnomAD3 genomes

AF:

0.0223

AC:

3397

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0111

Gnomad AMI

AF:

0.0275

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.0375

Gnomad EAS

AF:

0.0594

Gnomad SAS

AF:

0.125

Gnomad FIN

AF:

0.0180

Gnomad MID

AF:

0.0380

Gnomad NFE

AF:

0.0212

Gnomad OTH

AF:

0.0244

GnomAD3 exomes

AF:

0.0355

AC:

8922

AN:

251342

Hom.:

362

AF XY:

0.0399

AC XY:

5424

AN XY:

135876

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.00879

Gnomad ASJ exome

AF:

0.0391

Gnomad EAS exome

AF:

0.0570

Gnomad SAS exome

AF:

0.121

Gnomad FIN exome

AF:

0.0215

Gnomad NFE exome

AF:

0.0231

Gnomad OTH exome

AF:

0.0298

GnomAD4 exome

AF:

0.0291

AC:

42509

AN:

1461720

Hom.:

1248

Cov.:

AF XY:

0.0318

AC XY:

23159

AN XY:

727160

show subpopulations

Gnomad4 AFR exome

AF:

0.0118

Gnomad4 AMR exome

AF:

0.00868

Gnomad4 ASJ exome

AF:

0.0395

Gnomad4 EAS exome

AF:

0.0724

Gnomad4 SAS exome

AF:

0.118

Gnomad4 FIN exome

AF:

0.0217

Gnomad4 NFE exome

AF:

0.0220

Gnomad4 OTH exome

AF:

0.0302

GnomAD4 genome

AF:

0.0224

AC:

3408

AN:

152310

Hom.:

Cov.:

AF XY:

0.0235

AC XY:

1753

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0111

Gnomad4 AMR

AF:

0.0114

Gnomad4 ASJ

AF:

0.0375

Gnomad4 EAS

AF:

0.0595

Gnomad4 SAS

AF:

0.125

Gnomad4 FIN

AF:

0.0180

Gnomad4 NFE

AF:

0.0212

Gnomad4 OTH

AF:

0.0284

Alfa

AF:

0.0219

Hom.:

Bravo

AF:

0.0190

Asia WGS

AF:

0.122

AC:

424

AN:

3478

EpiCase

AF:

0.0232

EpiControl

AF:

0.0224

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Eurofins Ntd Llc (ga)

Dec 02, 2014

- -

Charcot-Marie-Tooth disease

Benign:1

Benign, criteria provided, single submitter

clinical testing

Molecular Genetics Laboratory, London Health Sciences Centre

- -

Charcot-Marie-Tooth disease type 2

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.89

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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