3-151385282-T-G

Variant names:

• chr3-151385282-T-G
• rs4603933
• NM_001393769.1:c.5088+91T>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.5088+91T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.878 in 719,884 control chromosomes in the GnomAD database, including 278,324 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 0.90 (61499 hom., cov: 31)
  • Exomes 𝑓: 0.87 (216825 hom.)
• Consequence: MED12L NM_001393769.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.293
• Publications: 7 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.954 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED12L	NM_001393769.1	c.5088+91T>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.5088+91T>G		intron_variant	Intron 36 of 44		NM_001393769.1	ENSP00000508695.1
MED12L	ENST00000474524.5	c.4983+91T>G		intron_variant	Intron 34 of 42	1		ENSP00000417235.1
MED12L	ENST00000273432.8	c.4563+91T>G		intron_variant	Intron 32 of 36	2		ENSP00000273432.4
MED12L	ENST00000686666.1	c.*119T>G		downstream_gene_variant				ENSP00000509482.1

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136528 AN: 152028 Hom.: 61450 Cov.: 31

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.896

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.826

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.894

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.867

Gnomad OTH AF: 0.909

GnomAD4 exome AF: 0.873 AC: 495781 AN: 567738 Hom.: 216825 AF XY: 0.876 AC XY: 257250 AN XY: 293770

African (AFR) AF: 0.964 AC: 11697 AN: 12134

American (AMR) AF: 0.906 AC: 11580 AN: 12784

Ashkenazi Jewish (ASJ) AF: 0.891 AC: 12254 AN: 13746

East Asian (EAS) AF: 0.838 AC: 22552 AN: 26900

South Asian (SAS) AF: 0.915 AC: 34450 AN: 37666

European-Finnish (FIN) AF: 0.889 AC: 36906 AN: 41532

Middle Eastern (MID) AF: 0.945 AC: 1989 AN: 2104

European-Non Finnish (NFE) AF: 0.864 AC: 339151 AN: 392406

Other (OTH) AF: 0.885 AC: 25202 AN: 28466

GnomAD4 genome AF: 0.898 AC: 136637 AN: 152146 Hom.: 61499 Cov.: 31 AF XY: 0.901 AC XY: 66992 AN XY: 74394

African (AFR) AF: 0.961 AC: 39910 AN: 41512

American (AMR) AF: 0.896 AC: 13689 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.882 AC: 3064 AN: 3472

East Asian (EAS) AF: 0.827 AC: 4282 AN: 5178

South Asian (SAS) AF: 0.910 AC: 4384 AN: 4816

European-Finnish (FIN) AF: 0.894 AC: 9448 AN: 10564

Middle Eastern (MID) AF: 0.956 AC: 281 AN: 294

European-Non Finnish (NFE) AF: 0.867 AC: 58930 AN: 68000

Other (OTH) AF: 0.905 AC: 1915 AN: 2116

Alfa AF: 0.897 Hom.: 18482

Bravo AF: 0.901

Asia WGS AF: 0.864 AC: 2995 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.1
DANN	Benign	0.44
PhyloP100		-0.29
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: rs4603933; hg19: chr3-151103070;