17-4731835-GCG-ACC

Variant names:

• chr17-4731835-GCG-ACC
• NM_001001683.4:c.145_147delGCGinsACC
• MED11 p.Ala49Thr

Variant summary

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

The NM_001001683.4(MED11):​c.145_147delGCGinsACC​(p.Ala49Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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: MED11 NM_001001683.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.01
• 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 0 ACMG points.

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.145_147delGCGinsACC	p.Ala49Thr	missense	N/A	NP_001001683.1	Q9P086
	MED11	NM_001305000.2		c.145_147delGCGinsACC	p.Ala49Thr	missense	N/A	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.145_147delGCGinsACC	p.Ala49Thr	missense	N/A	ENSP00000293777.5	Q9P086
	MED11	ENST00000886211.1		c.181_183delGCGinsACC	p.Ala61Thr	missense	N/A	ENSP00000556270.1
	MED11	ENST00000573708.1	TSL:2	c.145_147delGCGinsACC	p.Ala49Thr	missense	N/A	ENSP00000459834.1	I3L2Q0

Frequencies

GnomAD3 genomes Cov.: 31

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.0

Splicing

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: chr17-4635130;