rs10507268

Variant names:

• chr12-116102422-G-A
• rs10507268
• NM_015335.5:c.396-5670C>T

Variant summary

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

The NM_015335.5(MED13L):​c.396-5670C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 152,030 control chromosomes in the GnomAD database, including 2,379 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 0.17 (2379 hom., cov: 32)
• Consequence: MED13L NM_015335.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.907
• 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, 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED13L	NM_015335.5	c.396-5670C>T		intron_variant	Intron 3 of 30	ENST00000281928.9	NP_056150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED13L	ENST00000281928.9	c.396-5670C>T		intron_variant	Intron 3 of 30	1	NM_015335.5	ENSP00000281928.3
MED13L	ENST00000650226.1	c.396-5670C>T		intron_variant	Intron 3 of 30			ENSP00000496981.1
MED13L	ENST00000548743.2	c.366-5670C>T		intron_variant	Intron 3 of 16	3		ENSP00000448553.2
MED13L	ENST00000647567.1	c.306-5670C>T		intron_variant	Intron 2 of 8			ENSP00000497136.1

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25589 AN: 151912 Hom.: 2373 Cov.: 32

Gnomad AFR AF: 0.0911

Gnomad AMI AF: 0.124

Gnomad AMR AF: 0.162

Gnomad ASJ AF: 0.243

Gnomad EAS AF: 0.160

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.201

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.168 AC: 25616 AN: 152030 Hom.: 2379 Cov.: 32 AF XY: 0.171 AC XY: 12736 AN XY: 74302

African (AFR) AF: 0.0916 AC: 3802 AN: 41488

American (AMR) AF: 0.162 AC: 2472 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.243 AC: 845 AN: 3472

East Asian (EAS) AF: 0.160 AC: 826 AN: 5158

South Asian (SAS) AF: 0.219 AC: 1052 AN: 4808

European-Finnish (FIN) AF: 0.222 AC: 2337 AN: 10546

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.201 AC: 13662 AN: 67964

Other (OTH) AF: 0.204 AC: 430 AN: 2108

Alfa AF: 0.194 Hom.: 12575

Bravo AF: 0.158

Asia WGS AF: 0.208 AC: 723 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	5.3
DANN	Benign	0.52
PhyloP100		0.91
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: rs10507268; hg19: chr12-116540227;