chr14-70584841-G-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005466.4(MED6):āc.713C>Gā(p.Pro238Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,678 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 6.8e-7 ( 0 hom. )
Consequence
MED6
NM_005466.4 missense
NM_005466.4 missense
Scores
5
11
3
Clinical Significance
Conservation
PhyloP100: 8.49
Genes affected
MED6 (HGNC:19970): (mediator complex subunit 6) Enables transcription coactivator activity. Acts upstream of or within positive regulation of transcription by RNA polymerase II. Located in nucleoplasm. Part of mediator complex. [provided by Alliance of Genome Resources, Apr 2022]
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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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED6 | NM_005466.4 | c.713C>G | p.Pro238Arg | missense_variant | 8/8 | ENST00000256379.10 | |
MED6 | NM_001284211.2 | c.713C>G | p.Pro238Arg | missense_variant | 8/9 | ||
MED6 | NM_001284209.2 | c.734C>G | p.Pro245Arg | missense_variant | 8/8 | ||
MED6 | NM_001284210.2 | c.*51C>G | 3_prime_UTR_variant | 7/7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED6 | ENST00000256379.10 | c.713C>G | p.Pro238Arg | missense_variant | 8/8 | 1 | NM_005466.4 | P4 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461678Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 727132
GnomAD4 exome
AF:
AC:
1
AN:
1461678
Hom.:
Cov.:
30
AF XY:
AC XY:
1
AN XY:
727132
Gnomad4 AFR exome
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GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 16, 2024 | The c.713C>G (p.P238R) alteration is located in exon 8 (coding exon 8) of the MED6 gene. This alteration results from a C to G substitution at nucleotide position 713, causing the proline (P) at amino acid position 238 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;.;T;.
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Uncertain
D
MutationAssessor
Uncertain
.;.;M;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D;D
REVEL
Uncertain
Sift
Uncertain
D;.;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
1.0
.;.;D;.
Vest4
MutPred
Loss of glycosylation at P238 (P = 0.0119);Loss of glycosylation at P238 (P = 0.0119);Loss of glycosylation at P238 (P = 0.0119);.;
MVP
MPC
0.91
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
No publications associated with this variant yet.