Genetic Variant NM_001317078.4:c.522G>T (chr11-57704768-C-A) – 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.522G>T(p.Lys174Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000194 in 1,393,684 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: not found (cov: 30)

Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

MED19
NM_001317078.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.47

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=0.2545482).

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.522G>T	p.Lys174Asn	missense	Exon 3 of 5	NP_001304007.2	J3KR33
MED19	NM_153450.4		c.522G>T	p.Lys174Asn	missense	Exon 3 of 4	NP_703151.3	A0JLT2-2
MED19	NR_157587.1		n.558G>T		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.522G>T	p.Lys174Asn	missense	Exon 3 of 5	ENSP00000416227.4	J3KR33
MED19	ENST00000337672.9	TSL:1	c.522G>T	p.Lys174Asn	missense	Exon 3 of 4	ENSP00000337340.4	A0JLT2-2
MED19	ENST00000534677.1	TSL:1	n.721G>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251460

AF XY:

0.0000294

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:

0.0000439

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000194

AC:

AN:

1393684

Hom.:

Cov.:

AF XY:

0.0000246

AC XY:

AN XY:

692302

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31694

American (AMR)

AF:

0.00

AC:

AN:

42562

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23638

East Asian (EAS)

AF:

0.00

AC:

AN:

34958

South Asian (SAS)

AF:

0.00

AC:

AN:

85604

European-Finnish (FIN)

AF:

0.0000209

AC:

AN:

47798

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5388

European-Non Finnish (NFE)

AF:

0.0000235

AC:

AN:

1066086

Other (OTH)

AF:

0.0000179

AC:

AN:

55956

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

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:

0.0000403

Hom.:

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Pathogenic

0.87

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.47

CADD

Uncertain

(source)

DANN

Uncertain

1.0

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.36

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.81

M_CAP

Benign

0.0052

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.55

PhyloP100

1.5

PrimateAI

Uncertain

0.69

REVEL

Benign

0.17

MVP

0.23

MPC

0.54

ClinPred

0.39

GERP RS

2.9

Mutation Taster

=33/67

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over