rs765984652

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004229.4(MED14):​c.2108G>T​(p.Arg703Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000912 in 1,096,275 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. 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. R703H) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)
Exomes 𝑓: 9.1e-7 ( 0 hom. 0 hem. )

Consequence

MED14
NM_004229.4 missense

Scores

4
8
5

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.86
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 Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MED14NM_004229.4 linkc.2108G>T p.Arg703Leu missense_variant Exon 17 of 31 ENST00000324817.6 NP_004220.2 O60244

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MED14ENST00000324817.6 linkc.2108G>T p.Arg703Leu missense_variant Exon 17 of 31 1 NM_004229.4 ENSP00000323720.1 O60244
MED14ENST00000496531.2 linkn.-33G>T upstream_gene_variant 5

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
9.12e-7
AC:
1
AN:
1096275
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
361695
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000331
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
23

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Pathogenic
0.35
D
BayesDel_noAF
Pathogenic
0.27
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.71
D
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.98
D
M_CAP
Uncertain
0.16
D
MetaRNN
Uncertain
0.69
D
MetaSVM
Benign
-0.85
T
MutationAssessor
Benign
1.7
L
PrimateAI
Uncertain
0.76
T
PROVEAN
Uncertain
-3.6
D
REVEL
Benign
0.24
Sift
Uncertain
0.015
D
Sift4G
Uncertain
0.018
D
Polyphen
0.37
B
Vest4
0.73
MutPred
0.38
Loss of MoRF binding (P = 0.0664);
MVP
0.84
MPC
1.4
ClinPred
0.98
D
GERP RS
5.8
Varity_R
0.74
gMVP
0.81

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.12
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-40542198; API