Genetic Variant MED19:p.Arg183His (chr11-57704742-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_001317078.4(MED19):c.548G>A(p.Arg183His) variant causes a missense change. The variant allele was found at a frequency of 0.0000617 in 1,539,948 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 0.000091 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000059 ( 0 hom. )

Consequence

MED19
NM_001317078.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.93

Publications

3 publications found

Variant links:

Genes affected

MED19 (HGNC:29600): (mediator complex subunit 19) The protein encoded by this gene is a subunit of the Mediator complex, which binds to gene-specific regulatory factors and provides support for the basal RNA polymerase II transcription machinery. This gene has been implicated in the growth of several types of cancer, and inhibition of its expression inhibits the growth and spread of these cancers. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2015]

MED19 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=0.07512018).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001317078.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MED19	NM_001317078.4	MANE Select	c.548G>A	p.Arg183His	missense	Exon 3 of 5	NP_001304007.2	J3KR33
MED19	NM_153450.4		c.548G>A	p.Arg183His	missense	Exon 3 of 4	NP_703151.3	A0JLT2-2
MED19	NR_157587.1		n.584G>A		non_coding_transcript_exon	Exon 3 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MED19	ENST00000431606.5	TSL:1 MANE Select	c.548G>A	p.Arg183His	missense	Exon 3 of 5	ENSP00000416227.4	J3KR33
MED19	ENST00000337672.9	TSL:1	c.548G>A	p.Arg183His	missense	Exon 3 of 4	ENSP00000337340.4	A0JLT2-2
MED19	ENST00000917664.1		c.539G>A	p.Arg180His	missense	Exon 3 of 5	ENSP00000587723.1

Frequencies

GnomAD3 genomes

AF:

0.0000912

AC:

AN:

131624

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000457

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:

0.0000930

Gnomad OTH

AF:

0.000573

GnomAD2 exomes

AF:

0.0000835

AC:

AN:

251356

AF XY:

0.0000810

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000434

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000589

AC:

AN:

1408246

Hom.:

Cov.:

AF XY:

0.0000585

AC XY:

AN XY:

700422

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31988

American (AMR)

AF:

0.000416

AC:

AN:

43254

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24048

East Asian (EAS)

AF:

0.0000274

AC:

AN:

36458

South Asian (SAS)

AF:

0.0000466

AC:

AN:

85780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5260

European-Non Finnish (NFE)

AF:

0.0000502

AC:

AN:

1075276

Other (OTH)

AF:

0.000106

AC:

AN:

56738

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

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:

0.0000911

AC:

AN:

131702

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

61968

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

34932

American (AMR)

AF:

0.000457

AC:

AN:

10946

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3356

East Asian (EAS)

AF:

0.00

AC:

AN:

4466

South Asian (SAS)

AF:

0.00

AC:

AN:

3992

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6662

Middle Eastern (MID)

AF:

0.00

AC:

AN:

174

European-Non Finnish (NFE)

AF:

0.0000930

AC:

AN:

64538

Other (OTH)

AF:

0.000571

AC:

AN:

1752

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

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:

0.0000873

Hom.:

Bravo

AF:

0.000132

ExAC

AF:

0.0000741

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000237

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

-0.11

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.28

Eigen_PC

Uncertain

0.39

FATHMM_MKL

Uncertain

0.97

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.0075

MetaRNN

Benign

0.075

MetaSVM

Benign

-0.84

PhyloP100

6.9

PrimateAI

Uncertain

0.68

REVEL

Benign

0.15

MVP

0.20

MPC

1.5

ClinPred

0.12

GERP RS

5.1

Mutation Taster

=61/39

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

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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