X-71118549-A-G

Position:

• chrX-71118549-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000692304.1(MED12):​c.-206A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.55 (12781 hom., 17441 hem., cov: 22)
  • Exomes 𝑓: 0.47 (25492 hom. 51828 hem.)
  • Failed GnomAD Quality Control
• Consequence: MED12 ENST00000692304.1 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.46

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant X-71118549-A-G is Benign according to our data. Variant chrX-71118549-A-G is described in ClinVar as [Benign]. Clinvar id is 670932.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED12	NM_005120.3			upstream_gene_variant		ENST00000374080.8	NP_005111.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED12	ENST00000374080.8			upstream_gene_variant		1	NM_005120.3	ENSP00000363193	P4

Frequencies

GnomAD3 genomes AF: 0.550 AC: 60675 AN: 110285 Hom.: 12781 Cov.: 22 AF XY: 0.535 AC XY: 17383 AN XY: 32501

Gnomad AFR AF: 0.751

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.602

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.325

Gnomad SAS AF: 0.458

Gnomad FIN AF: 0.383

Gnomad MID AF: 0.626

Gnomad NFE AF: 0.461

Gnomad OTH AF: 0.574

GnomAD4 exome AF: 0.471 AC: 156103 AN: 331561 Hom.: 25492 Cov.: 3 AF XY: 0.470 AC XY: 51828 AN XY: 110233

Gnomad4 AFR exome AF: 0.751

Gnomad4 AMR exome AF: 0.606

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.323

Gnomad4 SAS exome AF: 0.476

Gnomad4 FIN exome AF: 0.391

Gnomad4 NFE exome AF: 0.458

Gnomad4 OTH exome AF: 0.509

GnomAD4 genome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.550 AC: 60731 AN: 110341 Hom.: 12781 Cov.: 22 AF XY: 0.536 AC XY: 17441 AN XY: 32567

Gnomad4 AFR AF: 0.751

Gnomad4 AMR AF: 0.601

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.325

Gnomad4 SAS AF: 0.458

Gnomad4 FIN AF: 0.383

Gnomad4 NFE AF: 0.461

Gnomad4 OTH AF: 0.581

Alfa AF: 0.484 Hom.: 39625

Bravo AF: 0.575

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 14, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	0.14
DANN	Benign	0.69

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11796153; hg19: chrX-70338399;