X-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-CCTCTT

Variant names:

• chrX-71132767-CCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT-C
• rs56658066
• NM_005120.3:c.4416-55_4416-16delCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_005120.3(MED12):​c.4416-55_4416-16delCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000138 in 653,429 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000011 (0 hom., 0 hem., cov: 0)
  • Exomes 𝑓: 0.000014 (0 hom. 4 hem.)
• Consequence: MED12 NM_005120.3 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High Hemizygotes in GnomAdExome4 at 4 XL gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED12	NM_005120.3	c.4416-55_4416-16delCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCT		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_4416-38delCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTTCTCTT		intron_variant	Intron 31 of 44	1	NM_005120.3	ENSP00000363193.3

Frequencies

GnomAD3 genomes AF: 0.0000110 AC: 1 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: 0.00

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: 0.0000219

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000142 AC: 8 AN: 562802 Hom.: 0 AF XY: 0.0000245 AC XY: 4 AN XY: 163154

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.0000704

Gnomad4 EAS exome AF: 0.0000429

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000110 AC: 1 AN: 90627 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 18709

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000219

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;