rs61748072

chr12-116019285-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_015335.5(MED13L):c.948G>A(p.Lys316=) 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
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.557

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 -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 GnomAd at 13 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED13L	NM_015335.5	c.948G>A	p.Lys316=	synonymous_variant	7/31	ENST00000281928.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED13L	ENST00000281928.9	c.948G>A	p.Lys316=	synonymous_variant	7/31	1	NM_015335.5	P1

Frequencies

GnomAD3 genomes AF: 0.0101 AC: 1543 AN: 152104 Hom.: 13 Cov.: 32

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.: 29 AF XY: 0.0107 AC XY: 1448 AN XY: 135580

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.: 31 AF XY: 0.0135 AC XY: 9831 AN XY: 727116

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.: 13 Cov.: 32 AF XY: 0.0101 AC XY: 752 AN XY: 74440

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.: 9

Bravo AF: 0.00981

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.0133

EpiControl AF: 0.0123

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 05, 2021

- -

Transposition of the great arteries, dextro-looped Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 30, 2024

- -

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

Other links and lift over

dbSNP: rs61748072; hg19: chr12-116457090; COSMIC: COSV56119883;