rs564143152

Variant names:

• chr12-116008385-CAG-C
• rs564143152
• NM_015335.5:c.2012+14_2012+15delCT

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP6_Very_Strong BS2

The NM_015335.5(MED13L):​c.2012+14_2012+15delCT 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
• Publications: 0 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]

MED13L Gene-Disease associations (from GenCC):

• cardiac anomalies - developmental delay - facial dysmorphism syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Illumina
• syndromic intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• congenital heart disease

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 Benign/Likely_benign. ClinVar VariationId is 445571.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 666 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.2012+14_2012+15delCT		intron	N/A	NP_056150.1	Q71F56

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED13L	ENST00000281928.9	TSL:1 MANE Select	c.2012+14_2012+15delCT		intron	N/A	ENSP00000281928.3	Q71F56
	MED13L	ENST00000650226.1		c.2012+14_2012+15delCT		intron	N/A	ENSP00000496981.1	A0A3B3IRX3
	MED13L	ENST00000649607.1		c.197+14_197+15delCT		intron	N/A	ENSP00000497064.1	A0A3B3IS46

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

GnomAD2 exomes AF: 0.00414 AC: 1002 AN: 242170 AF XY: 0.00395

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 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

African (AFR) AF: 0.00135 AC: 45 AN: 33220

American (AMR) AF: 0.00207 AC: 91 AN: 44012

Ashkenazi Jewish (ASJ) AF: 0.000199 AC: 5 AN: 25150

East Asian (EAS) AF: 0.00 AC: 0 AN: 39492

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84290

European-Finnish (FIN) AF: 0.00304 AC: 161 AN: 52888

Middle Eastern (MID) AF: 0.000244 AC: 1 AN: 4102

European-Non Finnish (NFE) AF: 0.00834 AC: 9195 AN: 1103104

Other (OTH) AF: 0.00618 AC: 368 AN: 59506

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

African (AFR) AF: 0.00135 AC: 56 AN: 41528

American (AMR) AF: 0.00255 AC: 39 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00311 AC: 33 AN: 10616

Middle Eastern (MID) AF: 0.00685 AC: 2 AN: 292

European-Non Finnish (NFE) AF: 0.00781 AC: 531 AN: 67990

Other (OTH) AF: 0.000950 AC: 2 AN: 2106

Alfa AF: 0.00542 Hom.: 1

Bravo AF: 0.00425

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Cardiac anomalies - developmental delay - facial dysmorphism syndrome (1)
-	-	1	not provided (1)
-	-	1	TRANSPOSITION OF THE GREAT ARTERIES, DEXTRO-LOOPED (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs564143152; hg19: chr12-116446190;