chr12-116148609-C-CTATATATATATATA

Variant names:

• chr12-116148609-C-CTATATATATATATA
• rs3043743
• NM_015335.5:c.311-37111_311-37098dupTATATATATATATA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_015335.5(MED13L):​c.311-37111_311-37098dupTATATATATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.000063 (0 hom., cov: 0)
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 9 AD gene.

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.311-37111_311-37098dupTATATATATATATA		intron	N/A	NP_056150.1	Q71F56
	MIR620	NR_030351.1		n.32_45dupTATATATATATATA		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.311-37111_311-37098dupTATATATATATATA		intron	N/A	ENSP00000281928.3	Q71F56
	MED13L	ENST00000650226.1		c.311-37111_311-37098dupTATATATATATATA		intron	N/A	ENSP00000496981.1	A0A3B3IRX3
	MED13L	ENST00000548743.2	TSL:3	c.281-37111_281-37098dupTATATATATATATA		intron	N/A	ENSP00000448553.2	F8VRB8

Frequencies

GnomAD3 genomes AF: 0.0000627 AC: 9 AN: 143470 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000280

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Cov.: 0

GnomAD4 genome AF: 0.0000627 AC: 9 AN: 143470 Hom.: 0 Cov.: 0 AF XY: 0.0000717 AC XY: 5 AN XY: 69692

African (AFR) AF: 0.000128 AC: 5 AN: 39026

American (AMR) AF: 0.000280 AC: 4 AN: 14284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3364

East Asian (EAS) AF: 0.00 AC: 0 AN: 4992

South Asian (SAS) AF: 0.00 AC: 0 AN: 4612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 65416

Other (OTH) AF: 0.00 AC: 0 AN: 1958

Alfa AF: 0.00 Hom.: 156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-2.5

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;