rs3732755

Positions:

• chr3-151193618-T-C

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001393769.1(MED12L):​c.2202T>C​(p.Tyr734=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0338 in 1,613,938 control chromosomes in the GnomAD database, including 3,509 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.086 (1288 hom., cov: 32)
  • Exomes 𝑓: 0.028 (2221 hom.)
• Consequence: MED12L NM_001393769.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.183

Genes affected

MED12L (HGNC:16050): (mediator complex subunit 12L) The protein encoded by this gene is part of the Mediator complex, which is involved in transcriptional coactivation of nearly all RNA polymerase II-dependent genes. The Mediator complex links gene-specific transcriptional activators with the basal transcription machinery. [provided by RefSeq, May 2010]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP7: Synonymous conserved (PhyloP=-0.183 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.224 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED12L	NM_001393769.1	c.2202T>C	p.Tyr734=	synonymous_variant	16/45	ENST00000687756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED12L	ENST00000687756.1	c.2202T>C	p.Tyr734=	synonymous_variant	16/45		NM_001393769.1	A2

Frequencies

GnomAD3 genomes AF: 0.0856 AC: 13027 AN: 152156 Hom.: 1280 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0564

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.00640

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0712

GnomAD3 exomes AF: 0.0561 AC: 14089 AN: 251314 Hom.: 1107 AF XY: 0.0523 AC XY: 7110 AN XY: 135830

Gnomad AFR exome AF: 0.243

Gnomad AMR exome AF: 0.0414

Gnomad ASJ exome AF: 0.0282

Gnomad EAS exome AF: 0.214

Gnomad SAS exome AF: 0.0864

Gnomad FIN exome AF: 0.00643

Gnomad NFE exome AF: 0.0129

Gnomad OTH exome AF: 0.0375

GnomAD4 exome AF: 0.0284 AC: 41508 AN: 1461664 Hom.: 2221 Cov.: 31 AF XY: 0.0294 AC XY: 21348 AN XY: 727148

Gnomad4 AFR exome AF: 0.233

Gnomad4 AMR exome AF: 0.0430

Gnomad4 ASJ exome AF: 0.0277

Gnomad4 EAS exome AF: 0.180

Gnomad4 SAS exome AF: 0.0836

Gnomad4 FIN exome AF: 0.00661

Gnomad4 NFE exome AF: 0.0122

Gnomad4 OTH exome AF: 0.0436

GnomAD4 genome AF: 0.0857 AC: 13048 AN: 152274 Hom.: 1288 Cov.: 32 AF XY: 0.0862 AC XY: 6419 AN XY: 74464

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.0564

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.0953

Gnomad4 FIN AF: 0.00640

Gnomad4 NFE AF: 0.0127

Gnomad4 OTH AF: 0.0705

Alfa AF: 0.0307 Hom.: 355

Bravo AF: 0.0955

Asia WGS AF: 0.118 AC: 411 AN: 3478

EpiCase AF: 0.0139

EpiControl AF: 0.0143

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.78
DANN	Benign	0.69

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs3732755; hg19: chr3-150911405; COSMIC: COSV56372745; COSMIC: COSV56372745;