NM_030973.4:c.16G>C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_030973.4(MED25):c.16G>C(p.Glu6Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000936 in 1,601,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000090 ( 0 hom. )

Consequence

MED25
NM_030973.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.95

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

congenital cataract-microcephaly-nevus flammeus simplex-severe intellectual disability syndrome
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
autosomal recessive non-syndromic intellectual disability
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Charcot-Marie-Tooth disease type 2B2
Inheritance: AR Classification: SUPPORTIVE, NO_KNOWN Submitted by: ClinGen, Orphanet

MED25 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.21017924).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030973.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED25	NM_030973.4	MANE Select	c.16G>C	p.Glu6Gln	missense	Exon 1 of 18	NP_112235.2	Q71SY5-1
	MED25	NM_001378355.1		c.16G>C	p.Glu6Gln	missense	Exon 1 of 18	NP_001365284.1	M0QZQ2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MED25	ENST00000312865.10	TSL:1 MANE Select	c.16G>C	p.Glu6Gln	missense	Exon 1 of 18	ENSP00000326767.5	Q71SY5-1
MED25	ENST00000538643.5	TSL:1	c.16G>C	p.Glu6Gln	missense	Exon 1 of 13	ENSP00000437496.1	Q71SY5-6
MED25	ENST00000595185.5	TSL:1	c.16G>C	p.Glu6Gln	missense	Exon 1 of 7	ENSP00000470027.1	M0QYR4

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152218

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

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

GnomAD2 exomes

AF:

0.00000887

AC:

AN:

225458

AF XY:

0.00000812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000118

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000897

AC:

AN:

1449678

Hom.:

Cov.:

AF XY:

0.0000111

AC XY:

AN XY:

720542

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33200

American (AMR)

AF:

0.00

AC:

AN:

42674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25914

East Asian (EAS)

AF:

0.000333

AC:

AN:

39082

South Asian (SAS)

AF:

0.00

AC:

AN:

85406

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51710

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5652

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1106184

Other (OTH)

AF:

0.00

AC:

AN:

59856

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152218

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41480

American (AMR)

AF:

0.00

AC:

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000193

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10618

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.00000830

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Charcot-Marie-Tooth disease type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.38

CADD

Pathogenic

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.036

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.31

FATHMM_MKL

Benign

0.49

LIST_S2

Uncertain

0.86

M_CAP

Pathogenic

0.45

MetaRNN

Benign

0.21

MetaSVM

Benign

-0.77

MutationAssessor

Benign

1.1

PhyloP100

2.0

PrimateAI

Pathogenic

0.91

PROVEAN

Benign

-0.45

REVEL

Benign

0.28

Sift

Pathogenic

0.0

Sift4G

Benign

0.21

Polyphen

0.065

Vest4

0.39

MutPred

0.14

Loss of glycosylation at S5 (P = 0.1075)

MVP

0.66

MPC

0.63

ClinPred

0.50

GERP RS

3.6

PromoterAI

-0.016

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.20

gMVP

0.36

Mutation Taster

=94/6

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over