Genetic Variant NM_001003891.3:c.654_656dupGCA (chr22-20564628-C-CCAG) – ACMG Classification: Benign (-7 pts)

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP3BP6_ModerateBS2

The NM_001003891.3(MED15):c.654_656dupGCA(p.Gln218dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00528 in 1,606,648 control chromosomes in the GnomAD database, including 28 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0049 ( 3 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 25 hom. )

Consequence

MED15
NM_001003891.3 disruptive_inframe_insertion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.48

Variant links:

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]

MED15 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP3

Nonframeshift variant in repetitive region in NM_001003891.3

BP6

Variant 22-20564628-C-CCAG is Benign according to our data. Variant chr22-20564628-C-CCAG is described in ClinVar as [Likely_benign]. Clinvar id is 2652902.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 735 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED15	NM_001003891.3 link	c.654_656dupGCA	p.Gln218dup	disruptive_inframe_insertion	Exon 6 of 18	ENST00000263205.11	NP_001003891.1	Q96RN5-1Q6PKB8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED15	ENST00000263205.11 link	c.654_656dupGCA	p.Gln218dup	disruptive_inframe_insertion	Exon 6 of 18	1	NM_001003891.3	ENSP00000263205.7		Q96RN5-1

Frequencies

GnomAD3 genomes

AF:

0.00487

AC:

735

AN:

150976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00329

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00851

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00155

Gnomad SAS

AF:

0.00272

Gnomad FIN

AF:

0.00230

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00590

Gnomad OTH

AF:

0.00964

GnomAD3 exomes

AF:

0.00526

AC:

1089

AN:

207078

Hom.:

AF XY:

0.00539

AC XY:

605

AN XY:

112274

show subpopulations

Gnomad AFR exome

AF:

0.00260

Gnomad AMR exome

AF:

0.00642

Gnomad ASJ exome

AF:

0.00242

Gnomad EAS exome

AF:

0.000950

Gnomad SAS exome

AF:

0.00442

Gnomad FIN exome

AF:

0.00340

Gnomad NFE exome

AF:

0.00687

Gnomad OTH exome

AF:

0.00541

GnomAD4 exome

AF:

0.00533

AC:

7751

AN:

1455554

Hom.:

Cov.:

AF XY:

0.00540

AC XY:

3912

AN XY:

724056

show subpopulations

Gnomad4 AFR exome

AF:

0.00283

Gnomad4 AMR exome

AF:

0.00553

Gnomad4 ASJ exome

AF:

0.00188

Gnomad4 EAS exome

AF:

0.000834

Gnomad4 SAS exome

AF:

0.00359

Gnomad4 FIN exome

AF:

0.00300

Gnomad4 NFE exome

AF:

0.00587

Gnomad4 OTH exome

AF:

0.00542

GnomAD4 genome

AF:

0.00486

AC:

735

AN:

151094

Hom.:

Cov.:

AF XY:

0.00471

AC XY:

348

AN XY:

73846

show subpopulations

Gnomad4 AFR

AF:

0.00328

Gnomad4 AMR

AF:

0.00843

Gnomad4 ASJ

AF:

0.00173

Gnomad4 EAS

AF:

0.00155

Gnomad4 SAS

AF:

0.00272

Gnomad4 FIN

AF:

0.00230

Gnomad4 NFE

AF:

0.00591

Gnomad4 OTH

AF:

0.00954

Bravo

AF:

0.00499

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MED15: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over