11-57712009-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001317078.4(MED19):​c.171G>T​(p.Lys57Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000131 in 1,531,244 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)
Exomes 𝑓: 7.3e-7 ( 0 hom. )

Consequence

MED19
NM_001317078.4 missense

Scores

1
2
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.763
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1792635).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MED19NM_001317078.4 linkc.171G>T p.Lys57Asn missense_variant Exon 1 of 5 ENST00000431606.5 NP_001304007.2 A0JLT2
MED19NM_153450.4 linkc.171G>T p.Lys57Asn missense_variant Exon 1 of 4 NP_703151.3 A0JLT2-2
MED19NR_157587.1 linkn.207G>T non_coding_transcript_exon_variant Exon 1 of 5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MED19ENST00000431606.5 linkc.171G>T p.Lys57Asn missense_variant Exon 1 of 5 1 NM_001317078.4 ENSP00000416227.4 J3KR33

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152214
Hom.:
0
Cov.:
33
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:
0.000192
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
GnomAD3 exomes
AF:
0.00000714
AC:
1
AN:
140052
Hom.:
0
AF XY:
0.0000134
AC XY:
1
AN XY:
74780
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000103
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
7.25e-7
AC:
1
AN:
1378912
Hom.:
0
Cov.:
31
AF XY:
0.00000147
AC XY:
1
AN XY:
678332
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.0000176
GnomAD4 genome
AF:
0.00000656
AC:
1
AN:
152332
Hom.:
0
Cov.:
33
AF XY:
0.0000134
AC XY:
1
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Nov 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.171G>T (p.K57N) alteration is located in exon 1 (coding exon 1) of the MED19 gene. This alteration results from a G to T substitution at nucleotide position 171, causing the lysine (K) at amino acid position 57 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Benign
-0.068
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
19
DANN
Uncertain
1.0
Eigen
Benign
0.11
Eigen_PC
Benign
0.096
FATHMM_MKL
Uncertain
0.94
D
LIST_S2
Benign
0.77
T;T
M_CAP
Benign
0.024
T
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-0.88
T
PrimateAI
Pathogenic
0.82
D
REVEL
Benign
0.089
MVP
0.30
MPC
0.95
ClinPred
0.87
D
GERP RS
3.0

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs575304143; hg19: chr11-57479481; API