Genetic Variant MED30:p.Pro5Ser (chr8-117520889-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_080651.4(MED30):c.13C>T(p.Pro5Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000587 in 1,600,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000039 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000061 ( 0 hom. )

Consequence

MED30
NM_080651.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.05

Publications

1 publications found

Variant links:

Genes affected

MED30 (HGNC:23032): (mediator complex subunit 30) The multiprotein TRAP/Mediator complex facilitates gene expression through a wide variety of transcriptional activators. MED30 is a component of this complex that appears to be metazoan specific (Baek et al., 2002 [PubMed 11909976]).[supplied by OMIM, Nov 2010]

MED30 links:

ENSG00000297933 (HGNC:):

ENSG00000297933 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.016767174).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080651.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MED30	NM_080651.4	MANE Select	c.13C>T	p.Pro5Ser	missense	Exon 1 of 4	NP_542382.1	Q96HR3-1
MED30	NM_001363182.2		c.13C>T	p.Pro5Ser	missense	Exon 1 of 4	NP_001350111.1
MED30	NM_001282986.2		c.13C>T	p.Pro5Ser	missense	Exon 1 of 3	NP_001269915.1	Q96HR3-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MED30	ENST00000297347.7	TSL:1 MANE Select	c.13C>T	p.Pro5Ser	missense	Exon 1 of 4	ENSP00000297347.3	Q96HR3-1
MED30	ENST00000522839.1	TSL:1	c.13C>T	p.Pro5Ser	missense	Exon 1 of 3	ENSP00000431051.1	Q96HR3-2
MED30	ENST00000920330.1		c.13C>T	p.Pro5Ser	missense	Exon 1 of 4	ENSP00000590389.1

Frequencies

GnomAD3 genomes

AF:

0.0000394

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000188

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000204

AC:

AN:

220060

AF XY:

0.000198

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000956

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000945

Gnomad OTH exome

AF:

0.000912

GnomAD4 exome

AF:

0.0000607

AC:

AN:

1448584

Hom.:

Cov.:

AF XY:

0.0000681

AC XY:

AN XY:

719354

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33100

American (AMR)

AF:

0.000882

AC:

AN:

43072

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25800

East Asian (EAS)

AF:

0.00

AC:

AN:

39124

South Asian (SAS)

AF:

0.00

AC:

AN:

85052

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51838

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4798

European-Non Finnish (NFE)

AF:

0.0000407

AC:

AN:

1106120

Other (OTH)

AF:

0.0000838

AC:

AN:

59680

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.528

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:

0.0000394

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.00

AC:

AN:

4838

European-Finnish (FIN)

AF:

0.000188

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000588

AC:

AN:

68044

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

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:

0.0000712

Hom.:

Bravo

AF:

0.0000491

ExAC

AF:

0.000218

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.043

BayesDel_noAF

Uncertain

0.090

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.056

Eigen

Uncertain

0.64

Eigen_PC

Uncertain

0.63

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

M_CAP

Benign

0.027

MetaRNN

Benign

0.017

MetaSVM

Benign

-0.35

MutationAssessor

Benign

1.6

PhyloP100

7.0

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.22

REVEL

Benign

0.27

Sift

Pathogenic

0.0

Sift4G

Benign

0.28

Polyphen

1.0

Vest4

0.54

MVP

0.22

MPC

1.5

ClinPred

0.19

GERP RS

5.5

PromoterAI

-0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.33

gMVP

0.73

Mutation Taster

=48/52

disease causing

(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