19-39392479-GCG-ACC

Variant names:

• chr19-39392479-GCG-ACC
• NM_017592.4:c.232_234delGCGinsACC
• MED29 p.Ala78Thr

Variant summary

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

The NM_017592.4(MED29):​c.232_234delGCGinsACC​(p.Ala78Thr) 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: 31)
• Consequence: MED29 NM_017592.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.96
• Publications: 0 publications found

Genes affected

MED29 (HGNC:23074): (mediator complex subunit 29) MED29 is a subunit of the Mediator complex, a multiprotein coactivator of RNA transcription that interacts with DNA-bound transcriptional activators, RNA polymerase II (see MIM 180660), and general initiation factors (Sato et al., 2003 [PubMed 14576168]).[supplied by OMIM, Aug 2009]

ENSG00000307007 (HGNC:):

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_017592.4. 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
	MED29	NM_017592.4	MANE Select	c.232_234delGCGinsACC	p.Ala78Thr	missense	N/A	NP_060062.2	Q9NX70-1
	MED29	NM_001317770.3		c.232_234delGCGinsACC	p.Ala78Thr	missense	N/A	NP_001304699.2	Q9NX70-2
	MED29	NR_133915.3		n.261+841_261+843delGCGinsACC		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED29	ENST00000315588.11	TSL:1 MANE Select	c.232_234delGCGinsACC	p.Ala78Thr	missense	N/A	ENSP00000314343.5	Q9NX70-1
	MED29	ENST00000615911.4	TSL:1	c.295_297delGCGinsACC	p.Ala99Thr	missense	N/A	ENSP00000481733.1	B4DUA7
	MED29	ENST00000596297.1	TSL:5	c.232_234delGCGinsACC	p.Ala78Thr	missense	N/A	ENSP00000473181.2	M0R3F3

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		8.0

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: chr19-39883119;