12-116148609-CTATATATATA-CTATA

Variant names:

• chr12-116148609-CTATATA-C
• rs3043743
• NM_015335.5:c.311-37103_311-37098delTATATA

Variant summary

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

The NM_015335.5(MED13L):​c.311-37103_311-37098delTATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0371 in 182,132 control chromosomes in the GnomAD database, including 171 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.035 (134 hom., cov: 0)
  • Exomes 𝑓: 0.044 (37 hom.)
• Consequence: MED13L NM_015335.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.466
• 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 (SAS) allele frequency at 95% confidence interval = 0.0538 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.311-37103_311-37098delTATATA		intron	N/A	NP_056150.1	Q71F56
	MIR620	NR_030351.1		n.40_45delTATATA		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.311-37103_311-37098delTATATA		intron	N/A	ENSP00000281928.3	Q71F56
	MED13L	ENST00000650226.1		c.311-37103_311-37098delTATATA		intron	N/A	ENSP00000496981.1	A0A3B3IRX3
	MED13L	ENST00000548743.2	TSL:3	c.281-37103_281-37098delTATATA		intron	N/A	ENSP00000448553.2	F8VRB8

Frequencies

GnomAD3 genomes AF: 0.0350 AC: 5016 AN: 143410 Hom.: 128 Cov.: 0

Gnomad AFR AF: 0.0316

Gnomad AMI AF: 0.0102

Gnomad AMR AF: 0.0276

Gnomad ASJ AF: 0.139

Gnomad EAS AF: 0.00741

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.0155

Gnomad MID AF: 0.0882

Gnomad NFE AF: 0.0360

Gnomad OTH AF: 0.0434

GnomAD2 exomes AF: 0.0452 AC: 1423 AN: 31506 AF XY: 0.0475

Gnomad AFR exome AF: 0.0716

Gnomad AMR exome AF: 0.0267

Gnomad ASJ exome AF: 0.115

Gnomad EAS exome AF: 0.0149

Gnomad FIN exome AF: 0.0217

Gnomad NFE exome AF: 0.0492

Gnomad OTH exome AF: 0.0520

GnomAD4 exome AF: 0.0444 AC: 1717 AN: 38704 Hom.: 37 AF XY: 0.0492 AC XY: 1103 AN XY: 22398

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

American (AMR) AF: 0.0370 AC: 60 AN: 1622

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 184 AN: 1794

East Asian (EAS) AF: 0.0433 AC: 9 AN: 208

South Asian (SAS) AF: 0.0731 AC: 434 AN: 5940

European-Finnish (FIN) AF: 0.0202 AC: 303 AN: 14986

Middle Eastern (MID) AF: 0.0820 AC: 10 AN: 122

European-Non Finnish (NFE) AF: 0.0506 AC: 656 AN: 12960

Other (OTH) AF: 0.0582 AC: 57 AN: 980

GnomAD4 genome AF: 0.0351 AC: 5033 AN: 143428 Hom.: 134 Cov.: 0 AF XY: 0.0350 AC XY: 2439 AN XY: 69704

African (AFR) AF: 0.0321 AC: 1256 AN: 39084

American (AMR) AF: 0.0276 AC: 394 AN: 14288

Ashkenazi Jewish (ASJ) AF: 0.139 AC: 467 AN: 3364

East Asian (EAS) AF: 0.00744 AC: 37 AN: 4976

South Asian (SAS) AF: 0.0596 AC: 274 AN: 4596

European-Finnish (FIN) AF: 0.0155 AC: 133 AN: 8600

Middle Eastern (MID) AF: 0.0857 AC: 24 AN: 280

European-Non Finnish (NFE) AF: 0.0360 AC: 2354 AN: 65386

Other (OTH) AF: 0.0432 AC: 85 AN: 1968

Alfa AF: 0.0148 Hom.: 156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.47
Mutation Taster		=100/0	polymorphism (auto)

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;