8-117539887-TC-GG

Variant names:

• chr8-117539887-TC-GG
• NM_080651.4:c.446_447delTCinsGG
• MED30 p.Leu149Arg

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_080651.4(MED30):​c.446_447delTCinsGG​(p.Leu149Arg) variant causes a missense change involving the alteration of a conserved nucleotide. 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: 32)
• Consequence: MED30 NM_080651.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.64
• Publications: 0 publications found

Genes affected

MED30 (HGNC:23032): (mediator complex subunit 30) The multiprotein TRAP/Mediator complex facilitates gene expression through a wide variety of transcriptional activators. MED30 is a component of this complex that appears to be metazoan specific (Baek et al., 2002 [PubMed 11909976]).[supplied by OMIM, Nov 2010]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_080651.4. 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
	MED30	NM_080651.4	MANE Select	c.446_447delTCinsGG	p.Leu149Arg	missense	N/A	NP_542382.1	Q96HR3-1
	MED30	NM_001282986.2		c.341_342delTCinsGG	p.Leu114Arg	missense	N/A	NP_001269915.1	Q96HR3-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED30	ENST00000297347.7	TSL:1 MANE Select	c.446_447delTCinsGG	p.Leu149Arg	missense	N/A	ENSP00000297347.3	Q96HR3-1
	MED30	ENST00000522839.1	TSL:1	c.341_342delTCinsGG	p.Leu114Arg	missense	N/A	ENSP00000431051.1	Q96HR3-2
	MED30	ENST00000920330.1		c.437_438delTCinsGG	p.Leu146Arg	missense	N/A	ENSP00000590389.1

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.6

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: chr8-118552126;