3-151398246-A-G

Position:

• chr3-151398246-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.5820+3379A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.506 in 152,014 control chromosomes in the GnomAD database, including 19,545 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 0.51 (19545 hom., cov: 32)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.628

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED12L	NM_001393769.1	c.5820+3379A>G		intron_variant		ENST00000687756.1	NP_001380698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED12L	ENST00000687756.1	c.5820+3379A>G		intron_variant			NM_001393769.1	ENSP00000508695.1
MED12L	ENST00000474524.5	c.5715+3379A>G		intron_variant		1		ENSP00000417235.1
MED12L	ENST00000273432.8	c.5295+3379A>G		intron_variant		2		ENSP00000273432.4
MED12L	ENST00000488092.1	n.201+3379A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.506 AC: 76871 AN: 151896 Hom.: 19527 Cov.: 32

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.648

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.544

Gnomad EAS AF: 0.534

Gnomad SAS AF: 0.483

Gnomad FIN AF: 0.538

Gnomad MID AF: 0.566

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.544

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

GnomAD4 genome AF: 0.506 AC: 76928 AN: 152014 Hom.: 19545 Cov.: 32 AF XY: 0.510 AC XY: 37872 AN XY: 74298

Gnomad4 AFR AF: 0.507

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.544

Gnomad4 EAS AF: 0.536

Gnomad4 SAS AF: 0.482

Gnomad4 FIN AF: 0.538

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.542

Alfa AF: 0.496 Hom.: 2355

Bravo AF: 0.507

Asia WGS AF: 0.501 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	12
DANN	Benign	0.36

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs17504; hg19: chr3-151116034;