22-20564628-CCAGCAGCAGCAGCAGCAG-CCAGCAG

Variant names:

• chr22-20564628-CCAGCAGCAGCAG-C
• rs374794651
• NM_001003891.3:c.645_656delGCAGCAGCAGCA

Variant summary

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

The NM_001003891.3(MED15):​c.645_656delGCAGCAGCAGCA​(p.Gln215_Gln218del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000703 in 1,606,700 control chromosomes in the GnomAD database, with no homozygous occurrence. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, 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.

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000042 (0 hom.)
• Consequence: MED15 NM_001003891.3 disruptive_inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.17
• Publications: 6 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 52 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.645_656delGCAGCAGCAGCA	p.Gln215_Gln218del	disruptive_inframe_deletion	Exon 6 of 18	NP_001003891.1	Q96RN5-1
	MED15	NM_015889.5		c.645_656delGCAGCAGCAGCA	p.Gln215_Gln218del	disruptive_inframe_deletion	Exon 6 of 17	NP_056973.2
	MED15	NM_001293234.2		c.645_656delGCAGCAGCAGCA	p.Gln215_Gln218del	disruptive_inframe_deletion	Exon 6 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.645_656delGCAGCAGCAGCA	p.Gln215_Gln218del	disruptive_inframe_deletion	Exon 6 of 18	ENSP00000263205.7	Q96RN5-1
	MED15	ENST00000292733.11	TSL:1	c.645_656delGCAGCAGCAGCA	p.Gln215_Gln218del	disruptive_inframe_deletion	Exon 6 of 17	ENSP00000292733.7	Q96RN5-2
	MED15	ENST00000406969.5	TSL:1	c.567_578delGCAGCAGCAGCA	p.Gln189_Gln192del	disruptive_inframe_deletion	Exon 6 of 17	ENSP00000384344.1	G3V1P5

Frequencies

GnomAD3 genomes AF: 0.000344 AC: 52 AN: 150978 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000659

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000135 AC: 28 AN: 207078 AF XY: 0.000116

Gnomad AFR exome AF: 0.00168

Gnomad AMR exome AF: 0.000174

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000110

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000419 AC: 61 AN: 1455604 Hom.: 0 AF XY: 0.0000428 AC XY: 31 AN XY: 724078

African (AFR) AF: 0.00114 AC: 38 AN: 33234

American (AMR) AF: 0.000135 AC: 6 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39574

South Asian (SAS) AF: 0.00 AC: 0 AN: 85784

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53048

Middle Eastern (MID) AF: 0.000174 AC: 1 AN: 5754

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1107512

Other (OTH) AF: 0.0000666 AC: 4 AN: 60102

GnomAD4 genome AF: 0.000344 AC: 52 AN: 151096 Hom.: 0 Cov.: 33 AF XY: 0.000325 AC XY: 24 AN XY: 73846

African (AFR) AF: 0.00117 AC: 48 AN: 41116

American (AMR) AF: 0.0000659 AC: 1 AN: 15186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4780

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10432

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.0000443 AC: 3 AN: 67662

Other (OTH) AF: 0.00 AC: 0 AN: 2096

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.000389

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.2
Mutation Taster		=106/94	disease causing (fs/PTC)

Splicing

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

Other links and lift over

dbSNP: rs374794651; hg19: chr22-20918915;