ENST00000263205.11:c.154_155insCCTA

Variant names:

• chr22-20537202-C-CCCTA
• NM_001003891.3:c.154_155insCCTA

Variant summary

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

The ENST00000263205.11(MED15):​c.154_155insCCTA​(p.Arg52ProfsTer2) variant causes a frameshift, stop gained, splice region 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. Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 34)
• Consequence: MED15 ENST00000263205.11 frameshift, stop_gained, splice_region
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.57
• Publications: 0 publications found

Genes affected

MED15 (HGNC:14248): (mediator complex subunit 15) The protein encoded by this gene is a subunit of the multiprotein complexes PC2 and ARC/DRIP and may function as a transcriptional coactivator in RNA polymerase II transcription. This gene contains stretches of trinucleotide repeats and is located in the chromosome 22 region which is deleted in DiGeorge syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jun 2014]

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: ENST00000263205.11. 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
	MED15	NM_001003891.3	MANE Select	c.154_155insCCTA	p.Arg52ProfsTer2	frameshift stop_gained splice_region	Exon 2 of 18	NP_001003891.1	Q96RN5-1
	MED15	NM_015889.5		c.154_155insCCTA	p.Arg52ProfsTer2	frameshift stop_gained splice_region	Exon 2 of 17	NP_056973.2
	MED15	NM_001293234.2		c.154_155insCCTA	p.Arg52ProfsTer2	frameshift stop_gained splice_region	Exon 2 of 17	NP_001280163.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED15	ENST00000263205.11	TSL:1 MANE Select	c.154_155insCCTA	p.Arg52ProfsTer2	frameshift stop_gained splice_region	Exon 2 of 18	ENSP00000263205.7	Q96RN5-1
	MED15	ENST00000292733.11	TSL:1	c.154_155insCCTA	p.Arg52ProfsTer2	frameshift stop_gained splice_region	Exon 2 of 17	ENSP00000292733.7	Q96RN5-2
	MED15	ENST00000406969.5	TSL:1	c.76_77insCCTA	p.Arg26ProfsTer2	frameshift stop_gained splice_region	Exon 2 of 17	ENSP00000384344.1	G3V1P5

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 34

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

Other links and lift over

hg19: chr22-20891489;