chr14-70584841-G-C

Variant summary

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

The NM_005466.4(MED6):ā€‹c.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

Scores

5
11
3

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.49
Variant links:
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]

Genome browser will be placed here

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
MED6NM_005466.4 linkuse as main transcriptc.713C>G p.Pro238Arg missense_variant 8/8 ENST00000256379.10
MED6NM_001284211.2 linkuse as main transcriptc.713C>G p.Pro238Arg missense_variant 8/9
MED6NM_001284209.2 linkuse as main transcriptc.734C>G p.Pro245Arg missense_variant 8/8
MED6NM_001284210.2 linkuse as main transcriptc.*51C>G 3_prime_UTR_variant 7/7

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
MED6ENST00000256379.10 linkuse as main transcriptc.713C>G p.Pro238Arg missense_variant 8/81 NM_005466.4 P4O75586-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461678
Hom.:
0
Cov.:
30
AF XY:
0.00000138
AC XY:
1
AN XY:
727132
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
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 submitterclinical testingAmbry GeneticsMay 16, 2024The 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: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.36
BayesDel_addAF
Pathogenic
0.25
D
BayesDel_noAF
Uncertain
0.12
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.26
.;.;T;.
Eigen
Pathogenic
0.81
Eigen_PC
Pathogenic
0.81
FATHMM_MKL
Pathogenic
1.0
D
LIST_S2
Uncertain
0.92
D;D;D;D
M_CAP
Benign
0.016
T
MetaRNN
Uncertain
0.67
D;D;D;D
MetaSVM
Uncertain
0.073
D
MutationAssessor
Uncertain
2.7
.;.;M;.
MutationTaster
Benign
1.0
D;D;D;D
PrimateAI
Uncertain
0.57
T
PROVEAN
Pathogenic
-5.2
D;.;D;D
REVEL
Uncertain
0.37
Sift
Uncertain
0.0040
D;.;D;D
Sift4G
Uncertain
0.0020
D;D;D;D
Polyphen
1.0
.;.;D;.
Vest4
0.78
MutPred
0.34
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
0.89
MPC
0.91
ClinPred
0.98
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.50
gMVP
0.43

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: chr14-71051558; API