rs141892892

Variant names:

• chr12-115984244-G-A
• rs141892892
• NM_015335.5:c.4467C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Moderate BP6_Very_Strong BS2

The NM_015335.5(MED13L):​c.4467C>T​(p.Ser1489Ser) variant causes a synonymous change. The variant allele was found at a frequency of 0.000893 in 1,613,816 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00087 (0 hom.)
• Consequence: MED13L NM_015335.5 synonymous
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 3.92
• 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 12-115984244-G-A is Benign according to our data. Variant chr12-115984244-G-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 533128.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 172 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.4467C>T	p.Ser1489Ser	synonymous	Exon 20 of 31	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.4467C>T	p.Ser1489Ser	synonymous	Exon 20 of 31	ENSP00000281928.3	Q71F56
	MED13L	ENST00000650226.1		c.4467C>T	p.Ser1489Ser	synonymous	Exon 20 of 31	ENSP00000496981.1	A0A3B3IRX3
	MED13L	ENST00000649607.1		c.2649C>T	p.Ser883Ser	synonymous	Exon 11 of 22	ENSP00000497064.1	A0A3B3IS46

Frequencies

GnomAD3 genomes AF: 0.00113 AC: 172 AN: 152098 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000193

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00419

Gnomad ASJ AF: 0.00403

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.00143

GnomAD2 exomes AF: 0.000810 AC: 203 AN: 250602 AF XY: 0.000716

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000841

Gnomad ASJ exome AF: 0.00308

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000926

Gnomad NFE exome AF: 0.00111

Gnomad OTH exome AF: 0.00180

GnomAD4 exome AF: 0.000868 AC: 1269 AN: 1461600 Hom.: 0 Cov.: 31 AF XY: 0.000850 AC XY: 618 AN XY: 727078

African (AFR) AF: 0.000149 AC: 5 AN: 33478

American (AMR) AF: 0.00112 AC: 50 AN: 44688

Ashkenazi Jewish (ASJ) AF: 0.00371 AC: 97 AN: 26128

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86212

European-Finnish (FIN) AF: 0.000150 AC: 8 AN: 53388

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.000931 AC: 1035 AN: 1111898

Other (OTH) AF: 0.00101 AC: 61 AN: 60378

GnomAD4 genome AF: 0.00113 AC: 172 AN: 152216 Hom.: 0 Cov.: 32 AF XY: 0.000941 AC XY: 70 AN XY: 74428

African (AFR) AF: 0.000193 AC: 8 AN: 41528

American (AMR) AF: 0.00419 AC: 64 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.00403 AC: 14 AN: 3470

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

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10602

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00122 AC: 83 AN: 68010

Other (OTH) AF: 0.00142 AC: 3 AN: 2114

Alfa AF: 0.00149 Hom.: 0

Bravo AF: 0.00143

EpiCase AF: 0.00158

EpiControl AF: 0.00101

ClinVar

ClinVar submissions

Significance: Benign/Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	1	TRANSPOSITION OF THE GREAT ARTERIES, DEXTRO-LOOPED (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	15
DANN	Benign	0.65
PhyloP100		3.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs141892892; hg19: chr12-116422049;