rs10507266

Variant names:

• chr12-116014770-T-C
• rs10507266
• NM_015335.5:c.1175+339A>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.1175+339A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0553 in 152,242 control chromosomes in the GnomAD database, including 301 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 0.055 (301 hom., cov: 32)
• Consequence: MED13L NM_015335.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77
• Publications: 3 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: Labcorp Genetics (formerly Invitae), Orphanet, Illumina, 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0781 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.1175+339A>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.1175+339A>G		intron	N/A	ENSP00000281928.3	Q71F56
	MED13L	ENST00000650226.1		c.1175+339A>G		intron	N/A	ENSP00000496981.1	A0A3B3IRX3
	MED13L	ENST00000549786.2	TSL:2	c.602+339A>G		intron	N/A	ENSP00000446782.2	H0YHC1

Frequencies

GnomAD3 genomes AF: 0.0553 AC: 8419 AN: 152124 Hom.: 300 Cov.: 32

Gnomad AFR AF: 0.0156

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0788

Gnomad ASJ AF: 0.0401

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0420

Gnomad FIN AF: 0.0527

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.0800

Gnomad OTH AF: 0.0421

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

GnomAD4 genome AF: 0.0553 AC: 8418 AN: 152242 Hom.: 301 Cov.: 32 AF XY: 0.0538 AC XY: 4008 AN XY: 74448

African (AFR) AF: 0.0156 AC: 648 AN: 41546

American (AMR) AF: 0.0790 AC: 1209 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.0401 AC: 139 AN: 3466

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5174

South Asian (SAS) AF: 0.0416 AC: 201 AN: 4832

European-Finnish (FIN) AF: 0.0527 AC: 559 AN: 10608

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.0799 AC: 5433 AN: 68000

Other (OTH) AF: 0.0416 AC: 88 AN: 2114

Alfa AF: 0.0684 Hom.: 665

Bravo AF: 0.0556

Asia WGS AF: 0.0310 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.11
DANN	Benign	0.29
PhyloP100		-1.8
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10507266;

hg19: chr12-116452575;