3-151398246-A-G

Variant names:

• chr3-151398246-A-G
• rs17504
• NM_001393769.1:c.5820+3379A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001393769.1. 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.5820+3379A>G		intron	N/A	NP_001380698.1
	MED12L	NM_053002.6		c.5715+3379A>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.5820+3379A>G		intron	N/A	ENSP00000508695.1
	MED12L	ENST00000474524.5	TSL:1	c.5715+3379A>G		intron	N/A	ENSP00000417235.1
	MED12L	ENST00000273432.8	TSL:2	c.5295+3379A>G		intron	N/A	ENSP00000273432.4

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

African (AFR) AF: 0.507 AC: 21013 AN: 41430

American (AMR) AF: 0.526 AC: 8037 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.544 AC: 1887 AN: 3470

East Asian (EAS) AF: 0.536 AC: 2768 AN: 5168

South Asian (SAS) AF: 0.482 AC: 2328 AN: 4826

European-Finnish (FIN) AF: 0.538 AC: 5682 AN: 10552

Middle Eastern (MID) AF: 0.568 AC: 167 AN: 294

European-Non Finnish (NFE) AF: 0.490 AC: 33313 AN: 67972

Other (OTH) AF: 0.542 AC: 1142 AN: 2108

Alfa AF: 0.497 Hom.: 2451

Bravo AF: 0.507

Asia WGS AF: 0.501 AC: 1744 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	12
DANN	Benign	0.36
PhyloP100		0.63
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17504; hg19: chr3-151116034;