NM_015335.5:c.311-37099_311-37098delTA

Variant names:

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

Variant summary

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

The NM_015335.5(MED13L):​c.311-37099_311-37098delTA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.301 in 180,914 control chromosomes in the GnomAD database, including 7,381 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.31 (7256 hom., cov: 0)
  • Exomes 𝑓: 0.25 (125 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 (EAS) allele frequency at 95% confidence interval = 0.493 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.311-37099_311-37098delTA		intron	N/A	NP_056150.1	Q71F56
	MIR620	NR_030351.1		n.44_45delTA		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.311-37099_311-37098delTA		intron	N/A	ENSP00000281928.3	Q71F56
	MED13L	ENST00000650226.1		c.311-37099_311-37098delTA		intron	N/A	ENSP00000496981.1	A0A3B3IRX3
	MED13L	ENST00000548743.2	TSL:3	c.281-37099_281-37098delTA		intron	N/A	ENSP00000448553.2	F8VRB8

Frequencies

GnomAD3 genomes AF: 0.313 AC: 44887 AN: 143214 Hom.: 7259 Cov.: 0

Gnomad AFR AF: 0.401

Gnomad AMI AF: 0.202

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.249

Gnomad EAS AF: 0.511

Gnomad SAS AF: 0.449

Gnomad FIN AF: 0.198

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.253

Gnomad OTH AF: 0.285

GnomAD2 exomes AF: 0.299 AC: 9420 AN: 31506 AF XY: 0.306

Gnomad AFR exome AF: 0.303

Gnomad AMR exome AF: 0.374

Gnomad ASJ exome AF: 0.284

Gnomad EAS exome AF: 0.401

Gnomad FIN exome AF: 0.258

Gnomad NFE exome AF: 0.291

Gnomad OTH exome AF: 0.279

GnomAD4 exome AF: 0.252 AC: 9514 AN: 37682 Hom.: 125 AF XY: 0.258 AC XY: 5625 AN XY: 21834

African (AFR) AF: 0.348 AC: 32 AN: 92

American (AMR) AF: 0.289 AC: 464 AN: 1606

Ashkenazi Jewish (ASJ) AF: 0.254 AC: 448 AN: 1766

East Asian (EAS) AF: 0.281 AC: 59 AN: 210

South Asian (SAS) AF: 0.343 AC: 2026 AN: 5912

European-Finnish (FIN) AF: 0.228 AC: 3261 AN: 14276

Middle Eastern (MID) AF: 0.267 AC: 31 AN: 116

European-Non Finnish (NFE) AF: 0.231 AC: 2935 AN: 12718

Other (OTH) AF: 0.262 AC: 258 AN: 986

GnomAD4 genome AF: 0.313 AC: 44893 AN: 143232 Hom.: 7256 Cov.: 0 AF XY: 0.318 AC XY: 22100 AN XY: 69598

African (AFR) AF: 0.400 AC: 15622 AN: 39026

American (AMR) AF: 0.337 AC: 4807 AN: 14254

Ashkenazi Jewish (ASJ) AF: 0.249 AC: 837 AN: 3360

East Asian (EAS) AF: 0.510 AC: 2536 AN: 4974

South Asian (SAS) AF: 0.450 AC: 2064 AN: 4586

European-Finnish (FIN) AF: 0.198 AC: 1704 AN: 8588

Middle Eastern (MID) AF: 0.268 AC: 75 AN: 280

European-Non Finnish (NFE) AF: 0.253 AC: 16509 AN: 65314

Other (OTH) AF: 0.285 AC: 560 AN: 1966

Alfa AF: 0.160 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: COSV56122391;