rs564143152

chr12-116008385-CAG-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_015335.5(MED13L):c.2012+14_2012+15del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00659 in 1,597,950 control chromosomes in the GnomAD database, including 51 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0068 (48 hom.)
• Consequence: MED13L NM_015335.5 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.163

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP6: Variant 12-116008385-CAG-C is Benign according to our data. Variant chr12-116008385-CAG-C is described in ClinVar as [Likely_benign]. Clinvar id is 445571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-116008385-CAG-C is described in Lovd as [Likely_benign].
• BS2: High Homozygotes in GnomAd at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED13L	NM_015335.5	c.2012+14_2012+15del		intron_variant		ENST00000281928.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED13L	ENST00000281928.9	c.2012+14_2012+15del		intron_variant		1	NM_015335.5	P1

Frequencies

GnomAD3 genomes AF: 0.00438 AC: 666 AN: 152068 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.00262

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00311

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00779

Gnomad OTH AF: 0.000960

GnomAD3 exomes AF: 0.00414 AC: 1002 AN: 242170 Hom.: 4 AF XY: 0.00395 AC XY: 516 AN XY: 130472

Gnomad AFR exome AF: 0.00197

Gnomad AMR exome AF: 0.00242

Gnomad ASJ exome AF: 0.000331

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00278

Gnomad NFE exome AF: 0.00737

Gnomad OTH exome AF: 0.00357

GnomAD4 exome AF: 0.00682 AC: 9867 AN: 1445764 Hom.: 48 AF XY: 0.00661 AC XY: 4738 AN XY: 717172

Gnomad4 AFR exome AF: 0.00135

Gnomad4 AMR exome AF: 0.00207

Gnomad4 ASJ exome AF: 0.000199

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000119

Gnomad4 FIN exome AF: 0.00304

Gnomad4 NFE exome AF: 0.00834

Gnomad4 OTH exome AF: 0.00618

GnomAD4 genome AF: 0.00438 AC: 666 AN: 152186 Hom.: 3 Cov.: 32 AF XY: 0.00395 AC XY: 294 AN XY: 74414

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00255

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00311

Gnomad4 NFE AF: 0.00781

Gnomad4 OTH AF: 0.000950

Alfa AF: 0.00542 Hom.: 1

Bravo AF: 0.00425

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Jun 29, 2017

- -

Cardiac anomalies - developmental delay - facial dysmorphism syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Fulgent Genetics, Fulgent Genetics

Oct 13, 2021

- -

Transposition of the great arteries, dextro-looped Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs564143152; hg19: chr12-116446190;