3-151324676-A-G

Variant names:

• chr3-151324676-A-G
• rs12107539
• NM_001393769.1:c.2251-25383A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000687756.1(MED12L):​c.2251-25383A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.309 in 152,044 control chromosomes in the GnomAD database, including 7,282 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 0.31 (7282 hom., cov: 32)
• Consequence: MED12L ENST00000687756.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0190
• Publications: 11 publications found

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]

MED12L Gene-Disease associations (from GenCC):

• Nizon-Isidor syndrome

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Illumina, Labcorp Genetics (formerly Invitae), Ambry Genetics
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000687756.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED12L	NM_001393769.1	MANE Select	c.2251-25383A>G		intron	N/A	NP_001380698.1
	MED12L	NM_053002.6		c.2146-25383A>G		intron	N/A	NP_443728.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED12L	ENST00000687756.1	MANE Select	c.2251-25383A>G		intron	N/A	ENSP00000508695.1
	MED12L	ENST00000474524.5	TSL:1	c.2146-25383A>G		intron	N/A	ENSP00000417235.1
	MED12L	ENST00000273432.8	TSL:2	c.1726-25383A>G		intron	N/A	ENSP00000273432.4

Frequencies

GnomAD3 genomes AF: 0.309 AC: 46902 AN: 151926 Hom.: 7284 Cov.: 32

Gnomad AFR AF: 0.310

Gnomad AMI AF: 0.260

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.200

Gnomad EAS AF: 0.224

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.237

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.306

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.309 AC: 46935 AN: 152044 Hom.: 7282 Cov.: 32 AF XY: 0.309 AC XY: 22977 AN XY: 74302

African (AFR) AF: 0.310 AC: 12858 AN: 41448

American (AMR) AF: 0.306 AC: 4680 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.200 AC: 694 AN: 3470

East Asian (EAS) AF: 0.224 AC: 1159 AN: 5172

South Asian (SAS) AF: 0.304 AC: 1464 AN: 4822

European-Finnish (FIN) AF: 0.367 AC: 3874 AN: 10568

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.313 AC: 21264 AN: 67976

Other (OTH) AF: 0.302 AC: 638 AN: 2112

Alfa AF: 0.310 Hom.: 3740

Bravo AF: 0.303

Asia WGS AF: 0.255 AC: 886 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.30
PhyloP100		0.019
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs12107539; hg19: chr3-151042464;