12-116148609-CTATATATATA-CTATATATATATATA

Variant names:

• chr12-116148609-C-CTATA
• rs3043743
• NM_015335.5:c.311-37101_311-37098dupTATA

Variant summary

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

The NM_015335.5(MED13L):​c.311-37101_311-37098dupTATA 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 0.025 (120 hom., cov: 0)
  • Exomes 𝑓: 0.0020 (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 (AFR) allele frequency at 95% confidence interval = 0.0742 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015335.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED13L	NM_015335.5	MANE Select	c.311-37101_311-37098dupTATA		intron	N/A	NP_056150.1	Q71F56
	MIR620	NR_030351.1		n.42_45dupTATA		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED13L	ENST00000281928.9	TSL:1 MANE Select	c.311-37101_311-37098dupTATA		intron	N/A	ENSP00000281928.3	Q71F56
	MED13L	ENST00000650226.1		c.311-37101_311-37098dupTATA		intron	N/A	ENSP00000496981.1	A0A3B3IRX3
	MED13L	ENST00000548743.2	TSL:3	c.281-37101_281-37098dupTATA		intron	N/A	ENSP00000448553.2	F8VRB8

Frequencies

GnomAD3 genomes AF: 0.0248 AC: 3551 AN: 143410 Hom.: 120 Cov.: 0

Gnomad AFR AF: 0.0766

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0147

Gnomad ASJ AF: 0.000892

Gnomad EAS AF: 0.00160

Gnomad SAS AF: 0.00282

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.00980

Gnomad NFE AF: 0.00428

Gnomad OTH AF: 0.0194

GnomAD2 exomes AF: 0.00375 AC: 118 AN: 31506 AF XY: 0.00324

Gnomad AFR exome AF: 0.0313

Gnomad AMR exome AF: 0.00495

Gnomad ASJ exome AF: 0.00456

Gnomad EAS exome AF: 0.00136

Gnomad FIN exome AF: 0.00170

Gnomad NFE exome AF: 0.00327

Gnomad OTH exome AF: 0.00839

GnomAD4 exome AF: 0.00204 AC: 81 AN: 39778 Hom.: 0 Cov.: 0 AF XY: 0.00213 AC XY: 49 AN XY: 22968

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

African (AFR) AF: 0.0326 AC: 3 AN: 92

American (AMR) AF: 0.00244 AC: 4 AN: 1642

Ashkenazi Jewish (ASJ) AF: 0.00334 AC: 6 AN: 1796

East Asian (EAS) AF: 0.00 AC: 0 AN: 210

South Asian (SAS) AF: 0.00215 AC: 13 AN: 6042

European-Finnish (FIN) AF: 0.00145 AC: 23 AN: 15838

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 124

European-Non Finnish (NFE) AF: 0.00222 AC: 29 AN: 13036

Other (OTH) AF: 0.00301 AC: 3 AN: 998

⚠️ 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: 0.0248 AC: 3552 AN: 143426 Hom.: 120 Cov.: 0 AF XY: 0.0235 AC XY: 1637 AN XY: 69698

African (AFR) AF: 0.0765 AC: 2988 AN: 39050

American (AMR) AF: 0.0147 AC: 210 AN: 14284

Ashkenazi Jewish (ASJ) AF: 0.000892 AC: 3 AN: 3364

East Asian (EAS) AF: 0.00161 AC: 8 AN: 4976

South Asian (SAS) AF: 0.00283 AC: 13 AN: 4598

European-Finnish (FIN) AF: 0.00104 AC: 9 AN: 8626

Middle Eastern (MID) AF: 0.0107 AC: 3 AN: 280

European-Non Finnish (NFE) AF: 0.00428 AC: 280 AN: 65398

Other (OTH) AF: 0.0193 AC: 38 AN: 1964

Alfa AF: 0.00156 Hom.: 156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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;