MED20 p.Met190Ile

Variant names:

• chr6-41907141-C-A
• NM_004275.5:c.570G>T
• MED20 p.Met190Ile

Your query was ambiguous. Multiple possible variants found:

• chr6-41907141-C-A
• chr6-41907141-C-G
• chr6-41907141-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_004275.5(MED20):​c.570G>T​(p.Met190Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: MED20 NM_004275.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.73
• Publications: 0 publications found

Genes affected

MED20 (HGNC:16840): (mediator complex subunit 20) This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. A mutation in this gene has been associated with a novel infantile-onset neurodegenerative movement disorder. Alternatively spliced transcript variants have been identified. [provided by RefSeq, Mar 2015]

ENSG00000288721 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004275.5. 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
	MED20	NM_004275.5	MANE Select	c.570G>T	p.Met190Ile	missense	Exon 4 of 4	NP_004266.2
	MED20	NM_001305455.2		c.384G>T	p.Met128Ile	missense	Exon 3 of 3	NP_001292384.1
	MED20	NM_001305456.2		c.384G>T	p.Met128Ile	missense	Exon 5 of 5	NP_001292385.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED20	ENST00000265350.9	TSL:1 MANE Select	c.570G>T	p.Met190Ile	missense	Exon 4 of 4	ENSP00000265350.4	Q9H944-1
	ENSG00000288721	ENST00000684631.1		n.570G>T		non_coding_transcript_exon	Exon 4 of 10	ENSP00000507261.1
	MED20	ENST00000953440.1		c.669G>T	p.Met223Ile	missense	Exon 5 of 5	ENSP00000623499.1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Pathogenic	0.20	D
BayesDel_noAF	Uncertain	0.050
CADD	Benign	20
DANN	Benign	0.97
DEOGEN2	Benign	0.041	T
Eigen	Benign	-0.045
Eigen_PC	Benign	0.18
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.0091	T
MetaRNN	Uncertain	0.50	D
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.98	L
PhyloP100		7.7
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.59	N
REVEL	Benign	0.18
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Varity_R		0.21
gMVP		0.80
Mutation Taster		=35/65	disease causing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr6-41874879;