12-116148609-CTATATATATA-CTATATA

Variant names:

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

Variant summary

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

The NM_015335.5(MED13L):​c.311-37101_311-37098delTATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 182,350 control chromosomes in the GnomAD database, including 3,348 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.20 (3016 hom., cov: 0)
  • Exomes 𝑓: 0.23 (332 hom.)
• Consequence: MED13L NM_015335.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.219
• 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 = 0.257 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_311-37098delTATA		intron	N/A	NP_056150.1	Q71F56
	MIR620	NR_030351.1		n.42_45delTATA		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_311-37098delTATA		intron	N/A	ENSP00000281928.3	Q71F56
	MED13L	ENST00000650226.1		c.311-37101_311-37098delTATA		intron	N/A	ENSP00000496981.1	A0A3B3IRX3
	MED13L	ENST00000548743.2	TSL:3	c.281-37101_281-37098delTATA		intron	N/A	ENSP00000448553.2	F8VRB8

Frequencies

GnomAD3 genomes AF: 0.204 AC: 29198 AN: 143308 Hom.: 3016 Cov.: 0

Gnomad AFR AF: 0.171

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.142

Gnomad EAS AF: 0.231

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.305

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.210

Gnomad OTH AF: 0.218

GnomAD2 exomes AF: 0.241 AC: 7602 AN: 31506 AF XY: 0.239

Gnomad AFR exome AF: 0.231

Gnomad AMR exome AF: 0.199

Gnomad ASJ exome AF: 0.143

Gnomad EAS exome AF: 0.317

Gnomad FIN exome AF: 0.281

Gnomad NFE exome AF: 0.214

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.229 AC: 8944 AN: 39024 Hom.: 332 AF XY: 0.232 AC XY: 5241 AN XY: 22560

African (AFR) AF: 0.130 AC: 12 AN: 92

American (AMR) AF: 0.180 AC: 289 AN: 1610

Ashkenazi Jewish (ASJ) AF: 0.134 AC: 236 AN: 1766

East Asian (EAS) AF: 0.296 AC: 61 AN: 206

South Asian (SAS) AF: 0.275 AC: 1628 AN: 5920

European-Finnish (FIN) AF: 0.266 AC: 4107 AN: 15458

Middle Eastern (MID) AF: 0.315 AC: 39 AN: 124

European-Non Finnish (NFE) AF: 0.186 AC: 2391 AN: 12866

Other (OTH) AF: 0.184 AC: 181 AN: 982

GnomAD4 genome AF: 0.204 AC: 29201 AN: 143326 Hom.: 3016 Cov.: 0 AF XY: 0.209 AC XY: 14531 AN XY: 69624

African (AFR) AF: 0.171 AC: 6669 AN: 39060

American (AMR) AF: 0.188 AC: 2680 AN: 14268

Ashkenazi Jewish (ASJ) AF: 0.142 AC: 477 AN: 3364

East Asian (EAS) AF: 0.231 AC: 1148 AN: 4968

South Asian (SAS) AF: 0.270 AC: 1238 AN: 4588

European-Finnish (FIN) AF: 0.305 AC: 2624 AN: 8598

Middle Eastern (MID) AF: 0.236 AC: 66 AN: 280

European-Non Finnish (NFE) AF: 0.210 AC: 13731 AN: 65346

Other (OTH) AF: 0.219 AC: 431 AN: 1968

Alfa AF: 0.181 Hom.: 156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.22
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: rs3043743; hg19: chr12-116586414; COSMIC: COSV56128230;