Variant 12-115969105-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_015335.5(MED13L):c.6068-8C>T variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 1,613,354 control chromosomes in the GnomAD database, including 219 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 13 hom., cov: 32)

Exomes 𝑓: 0.014 ( 206 hom. )

Consequence

MED13L
NM_015335.5 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.00005156

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.0630

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 12-115969105-G-A is Benign according to our data. Variant chr12-115969105-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 241045.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-115969105-G-A is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0141 (20659/1461180) while in subpopulation NFE AF= 0.016 (17752/1111604). AF 95% confidence interval is 0.0158. There are 206 homozygotes in gnomad4_exome. There are 10147 alleles in male gnomad4_exome subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED13L	NM_015335.5 linkuse as main transcript	c.6068-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000281928.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED13L	ENST00000281928.9 linkuse as main transcript	c.6068-8C>T		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		1	NM_015335.5	P1

Frequencies

GnomAD3 genomes

AF:

0.0105

AC:

1603

AN:

152056

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00300

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0147

Gnomad ASJ

AF:

0.00605

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.0156

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0151

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.0106

AC:

2657

AN:

250018

Hom.:

AF XY:

0.0108

AC XY:

1464

AN XY:

135216

show subpopulations

Gnomad AFR exome

AF:

0.00229

Gnomad AMR exome

AF:

0.0101

Gnomad ASJ exome

AF:

0.00678

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00465

Gnomad FIN exome

AF:

0.0141

Gnomad NFE exome

AF:

0.0145

Gnomad OTH exome

AF:

0.0189

GnomAD4 exome

AF:

0.0141

AC:

20659

AN:

1461180

Hom.:

206

Cov.:

AF XY:

0.0140

AC XY:

10147

AN XY:

726886

show subpopulations

Gnomad4 AFR exome

AF:

0.00224

Gnomad4 AMR exome

AF:

0.0105

Gnomad4 ASJ exome

AF:

0.00574

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00540

Gnomad4 FIN exome

AF:

0.0159

Gnomad4 NFE exome

AF:

0.0160

Gnomad4 OTH exome

AF:

0.0145

GnomAD4 genome

AF:

0.0105

AC:

1603

AN:

152174

Hom.:

Cov.:

AF XY:

0.0106

AC XY:

787

AN XY:

74404

show subpopulations

Gnomad4 AFR

AF:

0.00299

Gnomad4 AMR

AF:

0.0147

Gnomad4 ASJ

AF:

0.00605

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00436

Gnomad4 FIN

AF:

0.0156

Gnomad4 NFE

AF:

0.0151

Gnomad4 OTH

AF:

0.00994

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.0103

Asia WGS

AF:

0.00260

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 09, 2023

See Variant Classification Assertion Criteria. -

Transposition of the great arteries, dextro-looped

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

Intellectual disability

Benign:1

Likely benign, no assertion criteria provided

clinical testing

Institute of Human Genetics, University of Wuerzburg

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

1.3

DANN

Benign

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000052

dbscSNV1_RF

Benign

0.0040

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