Variant chr12-116019999-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_015335.5(MED13L):c.626-27A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0957 in 1,588,040 control chromosomes in the GnomAD database, including 8,308 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.076 ( 556 hom., cov: 32)

Exomes 𝑓: 0.098 ( 7752 hom. )

Consequence

MED13L
NM_015335.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0180

Variant links:

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 links:

MED13L (HGNC:):

MED13L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BP6

Variant 12-116019999-T-G is Benign according to our data. Variant chr12-116019999-T-G is described in ClinVar as [Benign]. Clinvar id is 1263826.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED13L	NM_015335.5 linkuse as main transcript	c.626-27A>C		intron_variant		ENST00000281928.9	NP_056150.1	Q71F56

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED13L	ENST00000281928.9 linkuse as main transcript	c.626-27A>C		intron_variant		1	NM_015335.5	ENSP00000281928.3		Q71F56

Frequencies

GnomAD3 genomes

AF:

0.0758

AC:

11526

AN:

152124

Hom.:

556

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0289

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.0766

Gnomad ASJ

AF:

0.120

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.0213

Gnomad FIN

AF:

0.0603

Gnomad MID

AF:

0.127

Gnomad NFE

AF:

0.112

Gnomad OTH

AF:

0.107

GnomAD3 exomes

AF:

0.0772

AC:

19234

AN:

249132

Hom.:

1001

AF XY:

0.0784

AC XY:

10550

AN XY:

134568

show subpopulations

Gnomad AFR exome

AF:

0.0268

Gnomad AMR exome

AF:

0.0600

Gnomad ASJ exome

AF:

0.122

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.0268

Gnomad FIN exome

AF:

0.0638

Gnomad NFE exome

AF:

0.113

Gnomad OTH exome

AF:

0.0985

GnomAD4 exome

AF:

0.0978

AC:

140403

AN:

1435798

Hom.:

7752

Cov.:

AF XY:

0.0962

AC XY:

68906

AN XY:

715970

show subpopulations

Gnomad4 AFR exome

AF:

0.0263

Gnomad4 AMR exome

AF:

0.0635

Gnomad4 ASJ exome

AF:

0.120

Gnomad4 EAS exome

AF:

0.000152

Gnomad4 SAS exome

AF:

0.0262

Gnomad4 FIN exome

AF:

0.0679

Gnomad4 NFE exome

AF:

0.111

Gnomad4 OTH exome

AF:

0.0964

GnomAD4 genome

AF:

0.0757

AC:

11525

AN:

152242

Hom.:

556

Cov.:

AF XY:

0.0712

AC XY:

5301

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0289

Gnomad4 AMR

AF:

0.0764

Gnomad4 ASJ

AF:

0.120

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.0211

Gnomad4 FIN

AF:

0.0603

Gnomad4 NFE

AF:

0.112

Gnomad4 OTH

AF:

0.106

Alfa

AF:

0.105

Hom.:

1202

Bravo

AF:

0.0772

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

8.8

DANN

Benign

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over