Genetic Variant MED13L:c.311-37105_311-37098delTATATATA (chr12-116148609-CTATATATA-C) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The NM_015335.5(MED13L):c.311-37105_311-37098delTATATATA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000316 in 183,258 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000091 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0011 ( 0 hom. )

Consequence

MED13L
NM_015335.5 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.466

Publications

3 publications found

Variant links:

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]

MED13L links:

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]

MIR620 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAd4 at 13 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.311-37105_311-37098delTATATATA		intron	N/A	NP_056150.1	Q71F56
	MIR620	NR_030351.1		n.38_45delTATATATA		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
MED13L	ENST00000281928.9	TSL:1 MANE Select	c.311-37105_311-37098delTATATATA	intron	N/A	ENSP00000281928.3	Q71F56
MED13L	ENST00000650226.1		c.311-37105_311-37098delTATATATA	intron	N/A	ENSP00000496981.1	A0A3B3IRX3
MED13L	ENST00000548743.2	TSL:3	c.281-37105_281-37098delTATATATA	intron	N/A	ENSP00000448553.2	F8VRB8

Frequencies

GnomAD3 genomes

AF:

0.0000906

AC:

AN:

143468

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000231

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000700

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000601

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

GnomAD2 exomes

AF:

0.000603

AC:

AN:

31506

AF XY:

0.000636

show subpopulations

Gnomad AFR exome

AF:

0.00302

Gnomad AMR exome

AF:

0.000990

Gnomad ASJ exome

AF:

0.00171

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000623

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00113

AC:

AN:

39774

Hom.:

AF XY:

0.00118

AC XY:

AN XY:

22960

show subpopulations

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

African (AFR)

AF:

0.0109

AC:

AN:

American (AMR)

AF:

0.00122

AC:

AN:

1640

Ashkenazi Jewish (ASJ)

AF:

0.00277

AC:

AN:

1802

East Asian (EAS)

AF:

0.00

AC:

AN:

210

South Asian (SAS)

AF:

0.00315

AC:

AN:

6028

European-Finnish (FIN)

AF:

0.00

AC:

AN:

15848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

124

European-Non Finnish (NFE)

AF:

0.00115

AC:

AN:

13030

Other (OTH)

AF:

0.00300

AC:

AN:

1000

⚠️ 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.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000906

AC:

AN:

143484

Hom.:

Cov.:

AF XY:

0.0000860

AC XY:

AN XY:

69728

show subpopulations

African (AFR)

AF:

0.000230

AC:

AN:

39092

American (AMR)

AF:

0.0000700

AC:

AN:

14290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3364

East Asian (EAS)

AF:

0.000603

AC:

AN:

4976

South Asian (SAS)

AF:

0.00

AC:

AN:

4598

European-Finnish (FIN)

AF:

0.00

AC:

AN:

8626

Middle Eastern (MID)

AF:

0.00

AC:

AN:

280

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

65404

Other (OTH)

AF:

0.00

AC:

AN:

1968

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

156

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.47

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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12-116148609-CTATATATATA-CTA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over