dbSNP rs377187824: MED22:p.Ala200Ser (chr9-133341510-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_133640.5(MED22):c.598G>T(p.Ala200Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000221 in 1,358,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 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. A200T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

MED22
NM_133640.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.38

Publications

0 publications found

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]

MED22 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.013276368).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133640.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED22	NM_133640.5	MANE Select	c.598G>T	p.Ala200Ser	missense	Exon 5 of 5	NP_598395.1	Q15528-1
	MED22	NM_181491.3		c.*2605G>T		3_prime_UTR	Exon 4 of 4	NP_852468.1	Q15528-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MED22	ENST00000343730.10	TSL:1 MANE Select	c.598G>T	p.Ala200Ser	missense	Exon 5 of 5	ENSP00000342343.5	Q15528-1
MED22	ENST00000610888.4	TSL:1	c.*2605G>T		3_prime_UTR	Exon 4 of 4	ENSP00000478773.1	Q15528-2
MED22	ENST00000614493.4	TSL:2	c.*2605G>T		3_prime_UTR	Exon 4 of 4	ENSP00000481493.1	Q15528-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000221

AC:

AN:

1358444

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

671316

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26984

American (AMR)

AF:

0.00

AC:

AN:

23128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22194

East Asian (EAS)

AF:

0.00

AC:

AN:

33074

South Asian (SAS)

AF:

0.00

AC:

AN:

69180

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51866

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4146

European-Non Finnish (NFE)

AF:

0.00000187

AC:

AN:

1072072

Other (OTH)

AF:

0.0000179

AC:

AN:

55800

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.408

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.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.065

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.011

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.017

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.65

M_CAP

Benign

0.014

MetaRNN

Benign

0.013

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.4

PhyloP100

-1.4

PrimateAI

Benign

0.36

PROVEAN

Benign

-0.24

REVEL

Benign

0.063

Sift

Benign

0.83

Sift4G

Benign

0.48

Polyphen

0.0

Vest4

0.029

MutPred

0.18

Gain of glycosylation at A200 (P = 0.0019)

MVP

0.17

ClinPred

0.56

GERP RS

-0.22

Varity_R

0.020

gMVP

0.20

Mutation Taster

=100/0

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