Genetic Variant NM_015335.5:c.948G>A (chr12-116019285-C-T) – ACMG Classification: Benign (-21 pts)

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_015335.5(MED13L):c.948G>A(p.Lys316Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 1,613,902 control chromosomes in the GnomAD database, including 213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.010 ( 13 hom., cov: 32)

Exomes 𝑓: 0.014 ( 200 hom. )

Consequence

MED13L
NM_015335.5 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.557

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 12-116019285-C-T is Benign according to our data. Variant chr12-116019285-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 241046.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.557 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0137 (20097/1461680) while in subpopulation NFE AF= 0.0155 (17267/1111900). AF 95% confidence interval is 0.0153. There are 200 homozygotes in gnomad4_exome. There are 9831 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED13L	NM_015335.5 link	c.948G>A	p.Lys316Lys	synonymous_variant	Exon 7 of 31	ENST00000281928.9	NP_056150.1	Q71F56

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED13L	ENST00000281928.9 link	c.948G>A	p.Lys316Lys	synonymous_variant	Exon 7 of 31	1	NM_015335.5	ENSP00000281928.3		Q71F56

Frequencies

GnomAD3 genomes

AF:

0.0101

AC:

1543

AN:

152104

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00297

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.0138

Gnomad ASJ

AF:

0.00576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.0154

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0145

Gnomad OTH

AF:

0.00911

GnomAD3 exomes

AF:

0.0105

AC:

2638

AN:

250916

Hom.:

AF XY:

0.0107

AC XY:

1448

AN XY:

135580

show subpopulations

Gnomad AFR exome

AF:

0.00221

Gnomad AMR exome

AF:

0.0100

Gnomad ASJ exome

AF:

0.00676

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00438

Gnomad FIN exome

AF:

0.0142

Gnomad NFE exome

AF:

0.0144

Gnomad OTH exome

AF:

0.0195

GnomAD4 exome

AF:

0.0137

AC:

20097

AN:

1461680

Hom.:

200

Cov.:

AF XY:

0.0135

AC XY:

9831

AN XY:

727116

show subpopulations

Gnomad4 AFR exome

AF:

0.00221

Gnomad4 AMR exome

AF:

0.0101

Gnomad4 ASJ exome

AF:

0.00578

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00481

Gnomad4 FIN exome

AF:

0.0159

Gnomad4 NFE exome

AF:

0.0155

Gnomad4 OTH exome

AF:

0.0143

GnomAD4 genome

AF:

0.0101

AC:

1543

AN:

152222

Hom.:

Cov.:

AF XY:

0.0101

AC XY:

752

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00296

Gnomad4 AMR

AF:

0.0137

Gnomad4 ASJ

AF:

0.00576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00414

Gnomad4 FIN

AF:

0.0154

Gnomad4 NFE

AF:

0.0145

Gnomad4 OTH

AF:

0.00901

Alfa

AF:

0.0124

Hom.:

Bravo

AF:

0.00981

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0133

EpiControl

AF:

0.0123

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 05, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Transposition of the great arteries, dextro-looped

Benign:1

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

7.6

DANN

Benign

0.67

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