rs10513398

Positions:

• chr3-151387443-A-G
• chr3-151387443-A-T

Variant summary

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

The NM_001393769.1(MED12L):​c.5089-367A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,034 control chromosomes in the GnomAD database, including 17,029 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 0.47 (17029 hom., cov: 32)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.154

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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.472 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED12L	NM_001393769.1	c.5089-367A>G		intron_variant		ENST00000687756.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED12L	ENST00000687756.1	c.5089-367A>G		intron_variant			NM_001393769.1	A2
MED12L	ENST00000474524.5	c.4984-367A>G		intron_variant		1		P4
MED12L	ENST00000273432.8	c.4564-367A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71677 AN: 151916 Hom.: 17021 Cov.: 32

Gnomad AFR AF: 0.464

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.531

Gnomad MID AF: 0.563

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.507

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

GnomAD4 genome AF: 0.472 AC: 71715 AN: 152034 Hom.: 17029 Cov.: 32 AF XY: 0.474 AC XY: 35238 AN XY: 74294

Gnomad4 AFR AF: 0.464

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.531

Gnomad4 EAS AF: 0.407

Gnomad4 SAS AF: 0.452

Gnomad4 FIN AF: 0.531

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.504

Alfa AF: 0.473 Hom.: 2145

Bravo AF: 0.465

Asia WGS AF: 0.415 AC: 1446 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.3
DANN	Benign	0.73

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: rs10513398; hg19: chr3-151105231;