17-4731892-C-G

Variant names:

• chr17-4731892-C-G
• rs771302700
• NM_001001683.4:c.202C>G

Variant summary

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

The NM_001001683.4(MED11):​c.202C>G​(p.Arg68Gly) variant causes a missense change. 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 variant affecting the same amino acid position, but resulting in a different missense (i.e. R68C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MED11 NM_001001683.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.62
• Publications: 0 publications found

Genes affected

MED11 (HGNC:32687): (mediator complex subunit 11) MED11 is a component of the Mediator complex, which is a coactivator for DNA-binding factors that activate transcription via RNA polymerase II (Sato et al., 2003 [PubMed 12584197]).[supplied by OMIM, Oct 2008]

MED11 Gene-Disease associations (from GenCC):

• neurodegeneration with developmental delay, early respiratory failure, myoclonic seizures, and brain abnormalities

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P

ENSG00000261898 (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_001001683.4. 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
	MED11	NM_001001683.4	MANE Select	c.202C>G	p.Arg68Gly	missense	Exon 2 of 3	NP_001001683.1	Q9P086
	MED11	NM_001305000.2		c.202C>G	p.Arg68Gly	missense	Exon 2 of 3	NP_001291929.1	I3L3E8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED11	ENST00000293777.6	TSL:1 MANE Select	c.202C>G	p.Arg68Gly	missense	Exon 2 of 3	ENSP00000293777.5	Q9P086
	MED11	ENST00000886211.1		c.238C>G	p.Arg80Gly	missense	Exon 2 of 3	ENSP00000556270.1
	MED11	ENST00000573708.1	TSL:2	c.202C>G	p.Arg68Gly	missense	Exon 2 of 2	ENSP00000459834.1	I3L2Q0

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Pathogenic	0.40	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.57
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.0083	T
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.9	M
PhyloP100		6.6
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.32
Sift	Benign	0.10	T
Sift4G	Benign	0.22	T
Polyphen		0.82	P
Vest4		0.88
MutPred		0.56		Loss of stability (P = 0.0256)
MVP		0.52
MPC		1.1
ClinPred		0.97	D
GERP RS		5.8
PromoterAI		-0.010	Neutral
Varity_R		0.54
gMVP		0.71

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

Other links and lift over

dbSNP: rs771302700; hg19: chr17-4635187;