rs201340945

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2

The NM_004229.4(MED14):​c.2354G>T​(p.Arg785Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000377 in 1,059,664 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 2 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R785H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 22)
Exomes 𝑓: 0.0000038 ( 0 hom. 2 hem. )

Consequence

MED14
NM_004229.4 missense

Scores

1
7
9

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.87
Variant links:
Genes affected
MED14 (HGNC:2370): (mediator complex subunit 14) The activation of gene transcription is a multistep process that is triggered by factors that recognize transcriptional enhancer sites in DNA. These factors work with co-activators to direct transcriptional initiation by the RNA polymerase II apparatus. The protein encoded by this gene is a subunit of the CRSP (cofactor required for SP1 activation) complex, which, along with TFIID, is required for efficient activation by SP1. This protein is also a component of other multisubunit complexes e.g. thyroid hormone receptor-(TR-) associated proteins which interact with TR and facilitate TR function on DNA templates in conjunction with initiation factors and cofactors. This protein contains a bipartite nuclear localization signal. This gene is known to escape chromosome X-inactivation. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.40967628).
BS2
High Hemizygotes in GnomAdExome4 at 2 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MED14NM_004229.4 linkc.2354G>T p.Arg785Leu missense_variant Exon 18 of 31 ENST00000324817.6 NP_004220.2 O60244

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MED14ENST00000324817.6 linkc.2354G>T p.Arg785Leu missense_variant Exon 18 of 31 1 NM_004229.4 ENSP00000323720.1 O60244
MED14ENST00000496531.2 linkn.214G>T non_coding_transcript_exon_variant Exon 2 of 5 5

Frequencies

GnomAD3 genomes
Cov.:
22
GnomAD4 exome
AF:
0.00000377
AC:
4
AN:
1059664
Hom.:
0
Cov.:
29
AF XY:
0.00000586
AC XY:
2
AN XY:
341144
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000487
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Uncertain
0.098
D
BayesDel_noAF
Benign
-0.10
CADD
Benign
22
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
T
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.94
D
M_CAP
Uncertain
0.15
D
MetaRNN
Benign
0.41
T
MetaSVM
Benign
-0.88
T
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.51
T
PROVEAN
Benign
-1.9
N
REVEL
Benign
0.12
Sift
Uncertain
0.017
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.055
B
Vest4
0.57
MutPred
0.33
Loss of loop (P = 0.2237);
MVP
0.64
MPC
1.1
ClinPred
0.83
D
GERP RS
4.9
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.48
gMVP
0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-40541866; API