X-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT

Position:

• chrX-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS1

The NM_005120.3(MED12):​c.4416-50_4416-16dupCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00019 (0 hom., 0 hem., cov: 0)
  • Exomes 𝑓: 0.00016 (1 hom. 36 hem.)
  • Failed GnomAD Quality Control
• Consequence: MED12 NM_005120.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294

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 Likely_benign. Variant got -4 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000188 (17/90627) while in subpopulation EAS AF= 0.000388 (1/2580). AF 95% confidence interval is 0.000168. There are 0 homozygotes in gnomad4. There are 0 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED12	NM_005120.3	c.4416-50_4416-16dupCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCT		intron_variant		ENST00000374080.8	NP_005111.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED12	ENST00000374080.8	c.4416-78_4416-77insCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT		intron_variant		1	NM_005120.3	ENSP00000363193.3

Frequencies

GnomAD3 genomes AF: 0.000188 AC: 17 AN: 90627 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 18709

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000248

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000388

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000261

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000285

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000156 AC: 88 AN: 562789 Hom.: 1 AF XY: 0.000221 AC XY: 36 AN XY: 163151

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000324

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000429

Gnomad4 SAS exome AF: 0.0000868

Gnomad4 FIN exome AF: 0.000239

Gnomad4 NFE exome AF: 0.000169

Gnomad4 OTH exome AF: 0.000110

GnomAD4 genome AF: 0.000188 AC: 17 AN: 90627 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 18709

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000388

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.000261

Gnomad4 NFE AF: 0.000285

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

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;