NM_005121.3:c.6117+349G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005121.3(MED13):​c.6117+349G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.156 in 152,144 control chromosomes in the GnomAD database, including 1,997 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.

Frequency

Genomes: 𝑓 0.16 ( 1997 hom., cov: 32)

Consequence

MED13
NM_005121.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.780

Publications

4 publications found
Variant links:
Genes affected
MED13 (HGNC:22474): (mediator complex subunit 13) This gene encodes a component of the mediator complex (also known as TRAP, SMCC, DRIP, or ARC), a transcriptional coactivator complex thought to be required for the expression of almost all genes. The mediator complex is recruited by transcriptional activators or nuclear receptors to induce gene expression, possibly by interacting with RNA polymerase II and promoting the formation of a transcriptional pre-initiation complex. The product of this gene is proposed to form a sub-complex with MED12, cyclin C, and CDK8 that can negatively regulate transactivation by mediator. [provided by RefSeq, Jul 2008]
MED13 Gene-Disease associations (from GenCC):
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • intellectual developmental disorder 61
    Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Illumina, Labcorp Genetics (formerly Invitae), G2P
  • syndromic intellectual disability
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MED13NM_005121.3 linkc.6117+349G>C intron_variant Intron 27 of 29 ENST00000397786.7 NP_005112.2 Q9UHV7A0A024QZ75
MED13XM_011525551.3 linkc.5958+349G>C intron_variant Intron 26 of 28 XP_011523853.1
MED13XM_011525553.4 linkc.5448+349G>C intron_variant Intron 24 of 26 XP_011523855.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MED13ENST00000397786.7 linkc.6117+349G>C intron_variant Intron 27 of 29 1 NM_005121.3 ENSP00000380888.2 Q9UHV7

Frequencies

GnomAD3 genomes
AF:
0.156
AC:
23778
AN:
152026
Hom.:
1999
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.178
Gnomad AMI
AF:
0.124
Gnomad AMR
AF:
0.161
Gnomad ASJ
AF:
0.206
Gnomad EAS
AF:
0.0645
Gnomad SAS
AF:
0.0803
Gnomad FIN
AF:
0.0907
Gnomad MID
AF:
0.316
Gnomad NFE
AF:
0.161
Gnomad OTH
AF:
0.193
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.156
AC:
23779
AN:
152144
Hom.:
1997
Cov.:
32
AF XY:
0.151
AC XY:
11226
AN XY:
74392
show subpopulations
African (AFR)
AF:
0.177
AC:
7354
AN:
41484
American (AMR)
AF:
0.161
AC:
2466
AN:
15296
Ashkenazi Jewish (ASJ)
AF:
0.206
AC:
716
AN:
3468
East Asian (EAS)
AF:
0.0645
AC:
334
AN:
5180
South Asian (SAS)
AF:
0.0799
AC:
385
AN:
4818
European-Finnish (FIN)
AF:
0.0907
AC:
960
AN:
10582
Middle Eastern (MID)
AF:
0.316
AC:
93
AN:
294
European-Non Finnish (NFE)
AF:
0.161
AC:
10954
AN:
68004
Other (OTH)
AF:
0.192
AC:
404
AN:
2108
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.503
Heterozygous variant carriers
0
1056
2112
3167
4223
5279
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
246
492
738
984
1230
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.149
Hom.:
234
Bravo
AF:
0.168
Asia WGS
AF:
0.0880
AC:
308
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
0.20
DANN
Benign
0.61
PhyloP100
-0.78
Mutation Taster
=100/0
polymorphism (auto)

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

Other links and lift over

dbSNP: rs12941827; hg19: chr17-60029977; API