12-116014770-T-C

Position:

• chr12-116014770-T-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED13L	NM_015335.5	c.1175+339A>G		intron_variant		ENST00000281928.9	NP_056150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED13L	ENST00000281928.9	c.1175+339A>G		intron_variant		1	NM_015335.5	ENSP00000281928	P1

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

Gnomad4 AFR AF: 0.0156

Gnomad4 AMR AF: 0.0790

Gnomad4 ASJ AF: 0.0401

Gnomad4 EAS AF: 0.00116

Gnomad4 SAS AF: 0.0416

Gnomad4 FIN AF: 0.0527

Gnomad4 NFE AF: 0.0799

Gnomad4 OTH AF: 0.0416

Alfa AF: 0.0694 Hom.: 538

Bravo AF: 0.0556

Asia WGS AF: 0.0310 AC: 106 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs10507266; hg19: chr12-116452575;