Genetic Variant MED19:p.Gly39Glu (chr11-57712064-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001317078.4(MED19):c.116G>A(p.Gly39Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000797 in 1,379,416 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/17 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G39V) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000080 ( 0 hom. )

Consequence

MED19
NM_001317078.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.59

Publications

0 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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.14793625).

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.116G>A	p.Gly39Glu	missense	Exon 1 of 5	NP_001304007.2	J3KR33
MED19	NM_153450.4		c.116G>A	p.Gly39Glu	missense	Exon 1 of 4	NP_703151.3	A0JLT2-2
MED19	NR_157587.1		n.152G>A		non_coding_transcript_exon	Exon 1 of 5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MED19	ENST00000431606.5	TSL:1 MANE Select	c.116G>A	p.Gly39Glu	missense	Exon 1 of 5	ENSP00000416227.4	J3KR33
MED19	ENST00000337672.9	TSL:1	c.116G>A	p.Gly39Glu	missense	Exon 1 of 4	ENSP00000337340.4	A0JLT2-2
MED19	ENST00000534677.1	TSL:1	n.158G>A		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000145

AC:

AN:

137918

AF XY:

0.0000135

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000194

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000797

AC:

AN:

1379416

Hom.:

Cov.:

AF XY:

0.00000442

AC XY:

AN XY:

679078

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30578

American (AMR)

AF:

0.00

AC:

AN:

32952

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24464

East Asian (EAS)

AF:

0.00

AC:

AN:

34658

South Asian (SAS)

AF:

0.0000128

AC:

AN:

77978

European-Finnish (FIN)

AF:

0.00

AC:

AN:

48122

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4216

European-Non Finnish (NFE)

AF:

0.00000935

AC:

AN:

1069532

Other (OTH)

AF:

0.00

AC:

AN:

56916

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.480

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.13

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.19

Eigen_PC

Benign

-0.040

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.79

M_CAP

Benign

0.012

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

PhyloP100

1.6

PrimateAI

Uncertain

0.71

REVEL

Benign

0.13

MVP

0.093

MPC

1.5

ClinPred

0.33

GERP RS

5.6

PromoterAI

-0.046

Neutral

(source)

Mutation Taster

=83/17

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over