rs11067880

Variant names:

• chr12-116022502-A-G
• rs11067880
• NM_015335.5:c.579T>C

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015335.5(MED13L):​c.579T>C​(p.Asn193Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00593 in 1,613,836 control chromosomes in the GnomAD database, including 462 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.032 (245 hom., cov: 32)
  • Exomes 𝑓: 0.0032 (217 hom.)
• Consequence: MED13L NM_015335.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.120
• Publications: 1 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, Illumina, Labcorp Genetics (formerly Invitae), G2P
• 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BP6: Variant 12-116022502-A-G is Benign according to our data. Variant chr12-116022502-A-G is described in ClinVar as Benign. ClinVar VariationId is 415972.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.12 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 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.579T>C	p.Asn193Asn	synonymous	Exon 5 of 31	NP_056150.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED13L	ENST00000281928.9	TSL:1 MANE Select	c.579T>C	p.Asn193Asn	synonymous	Exon 5 of 31	ENSP00000281928.3
	MED13L	ENST00000650226.1		c.579T>C	p.Asn193Asn	synonymous	Exon 5 of 31	ENSP00000496981.1
	MED13L	ENST00000549786.2	TSL:2	c.6T>C	p.Asn2Asn	synonymous	Exon 1 of 18	ENSP00000446782.2

Frequencies

GnomAD3 genomes AF: 0.0316 AC: 4809 AN: 152220 Hom.: 241 Cov.: 32

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0128

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.0205

GnomAD2 exomes AF: 0.00823 AC: 2063 AN: 250558 AF XY: 0.00606

Gnomad AFR exome AF: 0.110

Gnomad AMR exome AF: 0.00612

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000291

Gnomad OTH exome AF: 0.00344

GnomAD4 exome AF: 0.00324 AC: 4742 AN: 1461498 Hom.: 217 Cov.: 32 AF XY: 0.00270 AC XY: 1962 AN XY: 727022

African (AFR) AF: 0.112 AC: 3763 AN: 33460

American (AMR) AF: 0.00641 AC: 286 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39664

South Asian (SAS) AF: 0.000278 AC: 24 AN: 86206

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53386

Middle Eastern (MID) AF: 0.00434 AC: 25 AN: 5762

European-Non Finnish (NFE) AF: 0.000184 AC: 205 AN: 1111872

Other (OTH) AF: 0.00726 AC: 438 AN: 60368

GnomAD4 genome AF: 0.0317 AC: 4834 AN: 152338 Hom.: 245 Cov.: 32 AF XY: 0.0299 AC XY: 2225 AN XY: 74506

African (AFR) AF: 0.110 AC: 4573 AN: 41566

American (AMR) AF: 0.0128 AC: 196 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68028

Other (OTH) AF: 0.0203 AC: 43 AN: 2116

Alfa AF: 0.0120 Hom.: 126

Bravo AF: 0.0358

Asia WGS AF: 0.00779 AC: 29 AN: 3478

EpiCase AF: 0.000273

EpiControl AF: 0.000415

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	TRANSPOSITION OF THE GREAT ARTERIES, DEXTRO-LOOPED (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	6.5
DANN	Benign	0.67
PhyloP100		-0.12
PromoterAI		0.039	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs11067880; hg19: chr12-116460307;