chr9-133341657-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_133640.5(MED22):​c.451G>A​(p.Glu151Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000672 in 1,608,194 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 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000069 ( 0 hom. )

Consequence

MED22
NM_133640.5 missense

Scores

6
1
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.75
Variant links:
Genes affected
MED22 (HGNC:11477): (mediator complex subunit 22) This gene encodes a protein component of the mediator complex, which functions in the regulation of transcription by bridging interactions between gene-specific regulatory factors, RNA polymerase II, and general transcription factors. Alternatively spliced transcript variants encoding different isoforms have been observed. [provided by RefSeq, Jul 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3142138).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MED22NM_133640.5 linkc.451G>A p.Glu151Lys missense_variant Exon 5 of 5 ENST00000343730.10 NP_598395.1 Q15528-1A0A024R8C5
MED22NM_181491.3 linkc.*2458G>A 3_prime_UTR_variant Exon 4 of 4 NP_852468.1 Q15528-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MED22ENST00000343730.10 linkc.451G>A p.Glu151Lys missense_variant Exon 5 of 5 1 NM_133640.5 ENSP00000342343.5 Q15528-1
MED22ENST00000610888 linkc.*2458G>A 3_prime_UTR_variant Exon 4 of 4 1 ENSP00000478773.1 Q15528-2
MED22ENST00000614493 linkc.*2458G>A 3_prime_UTR_variant Exon 4 of 4 2 ENSP00000481493.1 Q15528-2
MED22ENST00000610672.4 linkc.451G>A p.Glu151Lys missense_variant Exon 5 of 5 2 ENSP00000482438.1 Q15528-1

Frequencies

GnomAD3 genomes
AF:
0.0000460
AC:
7
AN:
152228
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000385
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000412
AC:
10
AN:
242882
Hom.:
0
AF XY:
0.0000379
AC XY:
5
AN XY:
131774
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000915
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000694
AC:
101
AN:
1455848
Hom.:
0
Cov.:
29
AF XY:
0.0000539
AC XY:
39
AN XY:
724162
show subpopulations
Gnomad4 AFR exome
AF:
0.0000302
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000256
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000829
Gnomad4 OTH exome
AF:
0.0000997
GnomAD4 genome
AF:
0.0000459
AC:
7
AN:
152346
Hom.:
0
Cov.:
32
AF XY:
0.0000671
AC XY:
5
AN XY:
74490
show subpopulations
Gnomad4 AFR
AF:
0.0000240
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000386
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000416
ESP6500AA
AF:
0.00
AC:
0
ESP6500EA
AF:
0.000116
AC:
1
ExAC
AF:
0.0000576
AC:
7

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Apr 25, 2022
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.451G>A (p.E151K) alteration is located in exon 5 (coding exon 4) of the MED22 gene. This alteration results from a G to A substitution at nucleotide position 451, causing the glutamic acid (E) at amino acid position 151 to be replaced by a lysine (K). 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
0.11
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Pathogenic
0.31
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.049
T;T
Eigen
Benign
-0.037
Eigen_PC
Benign
0.13
FATHMM_MKL
Pathogenic
0.98
D
LIST_S2
Benign
0.86
.;D
M_CAP
Benign
0.036
D
MetaRNN
Benign
0.31
T;T
MetaSVM
Benign
-0.83
T
MutationAssessor
Benign
1.2
L;L
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
-0.78
.;N
REVEL
Benign
0.23
Sift
Pathogenic
0.0
.;D
Sift4G
Pathogenic
0.0
D;D
Polyphen
0.0060
B;B
Vest4
0.70
MVP
0.50
ClinPred
0.24
T
GERP RS
4.6
Varity_R
0.44
gMVP
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.070
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: rs373755320; hg19: chr9-136208507; COSMIC: COSV59297284; COSMIC: COSV59297284; API