chr3-151387443-A-G

Variant names:

• chr3-151387443-A-G
• rs10513398
• NM_001393769.1:c.5089-367A>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.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
• Publications: 8 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=-0.84).
• 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 rank	MANE	Protein	UniProt
MED12L	NM_001393769.1	c.5089-367A>G		intron_variant	Intron 36 of 44	ENST00000687756.1	NP_001380698.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED12L	ENST00000687756.1	c.5089-367A>G		intron_variant	Intron 36 of 44		NM_001393769.1	ENSP00000508695.1
MED12L	ENST00000474524.5	c.4984-367A>G		intron_variant	Intron 34 of 42	1		ENSP00000417235.1
MED12L	ENST00000273432.8	c.4564-367A>G		intron_variant	Intron 32 of 36	2		ENSP00000273432.4

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

African (AFR) AF: 0.464 AC: 19229 AN: 41472

American (AMR) AF: 0.429 AC: 6556 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1843 AN: 3470

East Asian (EAS) AF: 0.407 AC: 2108 AN: 5176

South Asian (SAS) AF: 0.452 AC: 2175 AN: 4812

European-Finnish (FIN) AF: 0.531 AC: 5595 AN: 10544

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

European-Non Finnish (NFE) AF: 0.477 AC: 32393 AN: 67978

Other (OTH) AF: 0.504 AC: 1062 AN: 2106

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
PhyloP100		0.15
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: rs10513398; hg19: chr3-151105231;