12-116148609-CTATATATATA-CTATATATATATA

Variant names:

• chr12-116148609-C-CTA
• rs3043743
• NM_015335.5:c.311-37099_311-37098dupTA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_015335.5(MED13L):​c.311-37099_311-37098dupTA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.049 (163 hom., cov: 0)
  • Exomes 𝑓: 0.043 (0 hom.)
• Consequence: MED13L NM_015335.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.54
• Publications: 3 publications found

Genes affected

MED13L (HGNC:22962): (mediator complex subunit 13L) The protein encoded by this gene is a subunit of the Mediator complex, a large complex of proteins that functions as a transcriptional coactivator for most RNA polymerase II-transcribed genes. The encoded protein is involved in early development of the heart and brain. Defects in this gene are a cause of transposition of the great arteries, dextro-looped (DTGA).[provided by RefSeq, Jul 2010]

MIR620 (HGNC:32876): (microRNA 620) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0541 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED13L	NM_015335.5	c.311-37099_311-37098dupTA		intron_variant	Intron 2 of 30	ENST00000281928.9	NP_056150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED13L	ENST00000281928.9	c.311-37099_311-37098dupTA		intron_variant	Intron 2 of 30	1	NM_015335.5	ENSP00000281928.3

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7013 AN: 143328 Hom.: 163 Cov.: 0

Gnomad AFR AF: 0.0358

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0573

Gnomad ASJ AF: 0.0640

Gnomad EAS AF: 0.0267

Gnomad SAS AF: 0.0291

Gnomad FIN AF: 0.0629

Gnomad MID AF: 0.0752

Gnomad NFE AF: 0.0548

Gnomad OTH AF: 0.0491

GnomAD2 exomes AF: 0.0522 AC: 1645 AN: 31506 AF XY: 0.0500

Gnomad AFR exome AF: 0.0192

Gnomad AMR exome AF: 0.0337

Gnomad ASJ exome AF: 0.0615

Gnomad EAS exome AF: 0.0163

Gnomad FIN exome AF: 0.0677

Gnomad NFE exome AF: 0.0542

Gnomad OTH exome AF: 0.0638

GnomAD4 exome AF: 0.0428 AC: 1670 AN: 38996 Hom.: 0 Cov.: 0 AF XY: 0.0390 AC XY: 878 AN XY: 22516

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.0435 AC: 4 AN: 92

American (AMR) AF: 0.0265 AC: 43 AN: 1624

Ashkenazi Jewish (ASJ) AF: 0.0546 AC: 97 AN: 1778

East Asian (EAS) AF: 0.0143 AC: 3 AN: 210

South Asian (SAS) AF: 0.0210 AC: 126 AN: 6000

European-Finnish (FIN) AF: 0.0527 AC: 809 AN: 15342

Middle Eastern (MID) AF: 0.0323 AC: 4 AN: 124

European-Non Finnish (NFE) AF: 0.0426 AC: 547 AN: 12836

Other (OTH) AF: 0.0374 AC: 37 AN: 990

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0489 AC: 7010 AN: 143346 Hom.: 163 Cov.: 0 AF XY: 0.0483 AC XY: 3362 AN XY: 69642

African (AFR) AF: 0.0358 AC: 1398 AN: 39062

American (AMR) AF: 0.0573 AC: 818 AN: 14270

Ashkenazi Jewish (ASJ) AF: 0.0640 AC: 215 AN: 3358

East Asian (EAS) AF: 0.0265 AC: 132 AN: 4974

South Asian (SAS) AF: 0.0289 AC: 133 AN: 4598

European-Finnish (FIN) AF: 0.0629 AC: 540 AN: 8588

Middle Eastern (MID) AF: 0.0750 AC: 21 AN: 280

European-Non Finnish (NFE) AF: 0.0548 AC: 3583 AN: 65364

Other (OTH) AF: 0.0488 AC: 96 AN: 1966

Alfa AF: 0.0215 Hom.: 156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.5
Mutation Taster		=100/0	polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3043743; hg19: chr12-116586414;