X-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT

Position:

• chrX-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_005120.3(MED12):​c.4416-40_4416-16dup 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 0.0049 (5 hom., 38 hem., cov: 0)
  • Exomes 𝑓: 0.0045 (27 hom. 829 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0049 (444/90663) while in subpopulation NFE AF= 0.00635 (290/45635). AF 95% confidence interval is 0.00575. There are 5 homozygotes in gnomad4. There are 38 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 5 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED12	NM_005120.3	c.4416-40_4416-16dup		intron_variant		ENST00000374080.8	NP_005111.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED12	ENST00000374080.8	c.4416-40_4416-16dup		intron_variant		1	NM_005120.3	ENSP00000363193	P4

Frequencies

GnomAD3 genomes AF: 0.00491 AC: 445 AN: 90623 Hom.: 5 Cov.: 0 AF XY: 0.00203 AC XY: 38 AN XY: 18709

Gnomad AFR AF: 0.00122

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00434

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00581

Gnomad SAS AF: 0.00370

Gnomad FIN AF: 0.0149

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00635

Gnomad OTH AF: 0.00336

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00449 AC: 2525 AN: 562556 Hom.: 27 AF XY: 0.00508 AC XY: 829 AN XY: 163072

Gnomad4 AFR exome AF: 0.000878

Gnomad4 AMR exome AF: 0.00663

Gnomad4 ASJ exome AF: 0.00162

Gnomad4 EAS exome AF: 0.00322

Gnomad4 SAS exome AF: 0.00310

Gnomad4 FIN exome AF: 0.0181

Gnomad4 NFE exome AF: 0.00365

Gnomad4 OTH exome AF: 0.00453

GnomAD4 genome AF: 0.00490 AC: 444 AN: 90663 Hom.: 5 Cov.: 0 AF XY: 0.00203 AC XY: 38 AN XY: 18749

Gnomad4 AFR AF: 0.00122

Gnomad4 AMR AF: 0.00421

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00584

Gnomad4 SAS AF: 0.00373

Gnomad4 FIN AF: 0.0149

Gnomad4 NFE AF: 0.00635

Gnomad4 OTH AF: 0.00331

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;