rs11611238

Positions:

• chr12-116019999-T-A
• chr12-116019999-T-C
• chr12-116019999-T-G

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015335.5(MED13L):​c.626-27A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000132 in 1,588,458 control chromosomes in the GnomAD database, including 1 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. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.00023 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00012 (1 hom.)
• Consequence: MED13L NM_015335.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0180

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 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• BP4: This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.74).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED13L	NM_015335.5	c.626-27A>T		intron_variant		ENST00000281928.9	NP_056150.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED13L	ENST00000281928.9	c.626-27A>T		intron_variant		1	NM_015335.5	ENSP00000281928.3

Frequencies

GnomAD3 genomes AF: 0.000230 AC: 35 AN: 152140 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00111

Gnomad ASJ AF: 0.00346

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000257 AC: 64 AN: 249132 Hom.: 1 AF XY: 0.000268 AC XY: 36 AN XY: 134568

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000525

Gnomad ASJ exome AF: 0.00289

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000125

Gnomad OTH exome AF: 0.000495

GnomAD4 exome AF: 0.000122 AC: 175 AN: 1436200 Hom.: 1 Cov.: 28 AF XY: 0.000121 AC XY: 87 AN XY: 716148

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000516

Gnomad4 ASJ exome AF: 0.00262

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000496

Gnomad4 OTH exome AF: 0.000453

GnomAD4 genome AF: 0.000230 AC: 35 AN: 152258 Hom.: 0 Cov.: 32 AF XY: 0.000228 AC XY: 17 AN XY: 74440

Gnomad4 AFR AF: 0.0000241

Gnomad4 AMR AF: 0.00111

Gnomad4 ASJ AF: 0.00346

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000920 Hom.: 1202

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	8.7
DANN	Benign	0.79
BranchPoint Hunter		3.0

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: rs11611238; hg19: chr12-116457804;