22-20566526-A-ACAGCAGCAG

Variant names:

• chr22-20566526-A-ACAGCAGCAG
• NM_001003891.3:c.778_786dupCAGCAGCAG

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP3 BS2

The NM_001003891.3(MED15):​c.778_786dupCAGCAGCAG​(p.Gln260_Gln262dup) variant causes a conservative inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00117 in 1,601,744 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0023 (1 hom., cov: 27)
  • Exomes 𝑓: 0.0011 (0 hom.)
• Consequence: MED15 NM_001003891.3 conservative_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.721
• 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]

ENSG00000307622 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP3: Nonframeshift variant in repetitive region in NM_001003891.3
• BS2: High AC in GnomAd4 at 343 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001003891.3. 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.778_786dupCAGCAGCAG	p.Gln260_Gln262dup	conservative_inframe_insertion	Exon 7 of 18	NP_001003891.1	Q96RN5-1
	MED15	NM_015889.5		c.778_786dupCAGCAGCAG	p.Gln260_Gln262dup	conservative_inframe_insertion	Exon 7 of 17	NP_056973.2
	MED15	NM_001293234.2		c.778_786dupCAGCAGCAG	p.Gln260_Gln262dup	conservative_inframe_insertion	Exon 7 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.778_786dupCAGCAGCAG	p.Gln260_Gln262dup	conservative_inframe_insertion	Exon 7 of 18	ENSP00000263205.7	Q96RN5-1
	MED15	ENST00000292733.11	TSL:1	c.778_786dupCAGCAGCAG	p.Gln260_Gln262dup	conservative_inframe_insertion	Exon 7 of 17	ENSP00000292733.7	Q96RN5-2
	MED15	ENST00000406969.5	TSL:1	c.700_708dupCAGCAGCAG	p.Gln234_Gln236dup	conservative_inframe_insertion	Exon 7 of 17	ENSP00000384344.1	G3V1P5

Frequencies

GnomAD3 genomes AF: 0.00226 AC: 340 AN: 150556 Hom.: 1 Cov.: 27

Gnomad AFR AF: 0.00272

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00555

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00137

Gnomad SAS AF: 0.00231

Gnomad FIN AF: 0.00537

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000978

Gnomad OTH AF: 0.00195

GnomAD4 exome AF: 0.00106 AC: 1537 AN: 1451076 Hom.: 0 Cov.: 26 AF XY: 0.00110 AC XY: 795 AN XY: 721976

African (AFR) AF: 0.00285 AC: 95 AN: 33376

American (AMR) AF: 0.00155 AC: 69 AN: 44540

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26054

East Asian (EAS) AF: 0.00174 AC: 69 AN: 39544

South Asian (SAS) AF: 0.00335 AC: 288 AN: 85880

European-Finnish (FIN) AF: 0.00489 AC: 251 AN: 51356

Middle Eastern (MID) AF: 0.00176 AC: 10 AN: 5694

European-Non Finnish (NFE) AF: 0.000617 AC: 682 AN: 1104652

Other (OTH) AF: 0.00117 AC: 70 AN: 59980

GnomAD4 genome AF: 0.00228 AC: 343 AN: 150668 Hom.: 1 Cov.: 27 AF XY: 0.00228 AC XY: 168 AN XY: 73528

African (AFR) AF: 0.00272 AC: 112 AN: 41224

American (AMR) AF: 0.00555 AC: 84 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3448

East Asian (EAS) AF: 0.00137 AC: 7 AN: 5114

South Asian (SAS) AF: 0.00210 AC: 10 AN: 4754

European-Finnish (FIN) AF: 0.00537 AC: 55 AN: 10248

Middle Eastern (MID) AF: 0.00345 AC: 1 AN: 290

European-Non Finnish (NFE) AF: 0.000978 AC: 66 AN: 67474

Other (OTH) AF: 0.00385 AC: 8 AN: 2076

Alfa AF: 0.000388 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.72
Mutation Taster		=66/34	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr22-20920813;