rs10513385

chr3-151182072-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001393769.1(MED12L):c.1495-3258A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.074 in 152,184 control chromosomes in the GnomAD database, including 955 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 0.074 (955 hom., cov: 32)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.134

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.192 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED12L	NM_001393769.1	c.1495-3258A>G		intron_variant		ENST00000687756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED12L	ENST00000687756.1	c.1495-3258A>G		intron_variant			NM_001393769.1	A2

Frequencies

GnomAD3 genomes AF: 0.0739 AC: 11244 AN: 152066 Hom.: 949 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0520

Gnomad ASJ AF: 0.0245

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.0390

Gnomad FIN AF: 0.00641

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0123

Gnomad OTH AF: 0.0603

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

GnomAD4 genome AF: 0.0740 AC: 11257 AN: 152184 Hom.: 955 Cov.: 32 AF XY: 0.0740 AC XY: 5506 AN XY: 74404

Gnomad4 AFR AF: 0.196

Gnomad4 AMR AF: 0.0519

Gnomad4 ASJ AF: 0.0245

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.0384

Gnomad4 FIN AF: 0.00641

Gnomad4 NFE AF: 0.0123

Gnomad4 OTH AF: 0.0597

Alfa AF: 0.0451 Hom.: 56

Bravo AF: 0.0839

Asia WGS AF: 0.0890 AC: 309 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	5.5
Dann	Benign	0.74

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

Publications

LitVar

Other links and lift over

dbSNP: rs10513385; hg19: chr3-150899859;