chr3-151388370-G-A

Variant names:

• chr3-151388370-G-A
• rs6798347
• NM_001393769.1:c.5451+198G>A

Variant summary

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

The NM_001393769.1(MED12L):​c.5451+198G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 151,992 control chromosomes in the GnomAD database, including 5,006 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 0.25 (5006 hom., cov: 32)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.896
• Publications: 16 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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED12L	NM_001393769.1	c.5451+198G>A		intron_variant	Intron 37 of 44	ENST00000687756.1	NP_001380698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED12L	ENST00000687756.1	c.5451+198G>A		intron_variant	Intron 37 of 44		NM_001393769.1	ENSP00000508695.1
MED12L	ENST00000474524.5	c.5346+198G>A		intron_variant	Intron 35 of 42	1		ENSP00000417235.1
MED12L	ENST00000273432.8	c.4926+198G>A		intron_variant	Intron 33 of 36	2		ENSP00000273432.4

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37984 AN: 151876 Hom.: 4998 Cov.: 32

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.383

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.250 AC: 38015 AN: 151992 Hom.: 5006 Cov.: 32 AF XY: 0.255 AC XY: 18961 AN XY: 74300

African (AFR) AF: 0.320 AC: 13257 AN: 41448

American (AMR) AF: 0.249 AC: 3796 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 483 AN: 3470

East Asian (EAS) AF: 0.291 AC: 1503 AN: 5162

South Asian (SAS) AF: 0.383 AC: 1845 AN: 4814

European-Finnish (FIN) AF: 0.222 AC: 2347 AN: 10556

Middle Eastern (MID) AF: 0.197 AC: 58 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14172 AN: 67954

Other (OTH) AF: 0.218 AC: 460 AN: 2108

Alfa AF: 0.242 Hom.: 2063

Bravo AF: 0.252

Asia WGS AF: 0.320 AC: 1113 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.2
DANN	Benign	0.66
PhyloP100		-0.90
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: rs6798347; hg19: chr3-151106158;