X-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-CCTCTTCTCTTCTCTT

Variant names:

• chrX-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-C
• rs56658066
• NM_005120.3:c.4416-45_4416-16delCTTCTCTTCTCTTCTCTTCTCTTCTCTTCT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_005120.3(MED12):​c.4416-45_4416-16delCTTCTCTTCTCTTCTCTTCTCTTCTCTTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.219 in 562,359 control chromosomes in the GnomAD database, including 15,649 homozygotes. There are 39,234 hemizygotes in GnomAD. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (2582 hom., 5311 hem., cov: 0)
  • Exomes 𝑓: 0.22 (15649 hom. 39234 hem.)
  • Failed GnomAD Quality Control
• Consequence: MED12 NM_005120.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.312

Genes affected

MED12 (HGNC:11957): (mediator complex subunit 12) The initiation of transcription is controlled in part by a large protein assembly known as the preinitiation complex. A component of this preinitiation complex is a 1.2 MDa protein aggregate called Mediator. This Mediator component binds with a CDK8 subcomplex which contains the protein encoded by this gene, mediator complex subunit 12 (MED12), along with MED13, CDK8 kinase, and cyclin C. The CDK8 subcomplex modulates Mediator-polymerase II interactions and thereby regulates transcription initiation and reinitation rates. The MED12 protein is essential for activating CDK8 kinase. Defects in this gene cause X-linked Opitz-Kaveggia syndrome, also known as FG syndrome, and Lujan-Fryns syndrome. [provided by RefSeq, Aug 2009]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant X-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-C is Benign according to our data. Variant chrX-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-C is described in ClinVar as [Benign]. Clinvar id is 95251.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (MID) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED12	NM_005120.3	c.4416-45_4416-16delCTTCTCTTCTCTTCTCTTCTCTTCTCTTCT		intron_variant	Intron 31 of 44	ENST00000374080.8	NP_005111.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED12	ENST00000374080.8	c.4416-77_4416-48delCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT		intron_variant	Intron 31 of 44	1	NM_005120.3	ENSP00000363193.3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 22704 AN: 90438 Hom.: 2584 Cov.: 0 AF XY: 0.286 AC XY: 5306 AN XY: 18552 FAILED QC

Gnomad AFR AF: 0.0814

Gnomad AMI AF: 0.417

Gnomad AMR AF: 0.219

Gnomad ASJ AF: 0.432

Gnomad EAS AF: 0.00426

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.493

Gnomad NFE AF: 0.347

Gnomad OTH AF: 0.299

GnomAD4 exome AF: 0.219 AC: 122883 AN: 562359 Hom.: 15649 AF XY: 0.241 AC XY: 39234 AN XY: 162735

Gnomad4 AFR exome AF: 0.0595

Gnomad4 AMR exome AF: 0.128

Gnomad4 ASJ exome AF: 0.358

Gnomad4 EAS exome AF: 0.00275

Gnomad4 SAS exome AF: 0.119

Gnomad4 FIN exome AF: 0.288

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.251 AC: 22700 AN: 90479 Hom.: 2582 Cov.: 0 AF XY: 0.286 AC XY: 5311 AN XY: 18593

Gnomad4 AFR AF: 0.0813

Gnomad4 AMR AF: 0.219

Gnomad4 ASJ AF: 0.432

Gnomad4 EAS AF: 0.00428

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.347

Gnomad4 OTH AF: 0.297

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

May 09, 2013

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Apr 23, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was found in TAADV2-WO-FBN1-PANCARD,TAADV2-PANCARD -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs56658066; hg19: chrX-70352617;