chr12-116261870-T-C

Variant names:

• chr12-116261870-T-C
• rs11615689
• NM_015335.5:c.72+15190A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015335.5(MED13L):​c.72+15190A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 152,240 control chromosomes in the GnomAD database, including 1,938 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (1938 hom., cov: 32)
• Consequence: MED13L NM_015335.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.256
• Publications: 7 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.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.205 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.72+15190A>G		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.72+15190A>G		intron	N/A	ENSP00000281928.3	Q71F56
	MED13L	ENST00000650226.1		c.72+15190A>G		intron	N/A	ENSP00000496981.1	A0A3B3IRX3
	MED13L	ENST00000548743.2	TSL:3	c.42+14560A>G		intron	N/A	ENSP00000448553.2	F8VRB8

Frequencies

GnomAD3 genomes AF: 0.149 AC: 22640 AN: 152122 Hom.: 1935 Cov.: 32

Gnomad AFR AF: 0.0678

Gnomad AMI AF: 0.155

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.138

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.215

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.183

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.149 AC: 22653 AN: 152240 Hom.: 1938 Cov.: 32 AF XY: 0.152 AC XY: 11337 AN XY: 74442

African (AFR) AF: 0.0680 AC: 2825 AN: 41540

American (AMR) AF: 0.148 AC: 2261 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.138 AC: 480 AN: 3470

East Asian (EAS) AF: 0.155 AC: 806 AN: 5184

South Asian (SAS) AF: 0.215 AC: 1040 AN: 4828

European-Finnish (FIN) AF: 0.216 AC: 2296 AN: 10606

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.182 AC: 12350 AN: 68008

Other (OTH) AF: 0.184 AC: 389 AN: 2110

Alfa AF: 0.172 Hom.: 1693

Bravo AF: 0.136

Asia WGS AF: 0.204 AC: 709 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.9
DANN	Benign	0.30
PhyloP100		0.26
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: rs11615689; hg19: chr12-116699675;