chr17-39409147-C-T
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2BP4_StrongBS2
The NM_004774.4(MED1):c.3074G>A(p.Ser1025Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000886 in 1,614,158 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000047 ( 1 hom. )
Consequence
MED1
NM_004774.4 missense
NM_004774.4 missense
Scores
2
6
11
Clinical Significance
Conservation
PhyloP100: 7.56
Genes affected
MED1 (HGNC:9234): (mediator complex subunit 1) 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. It also regulates p53-dependent apoptosis and it is essential for adipogenesis. This protein is known to have the ability to self-oligomerize. [provided by RefSeq, Jul 2008]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, MED1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.017335117).
BS2
?
High AC in GnomAd at 76 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MED1 | NM_004774.4 | c.3074G>A | p.Ser1025Asn | missense_variant | 17/17 | ENST00000300651.11 | |
MED1 | XM_047436314.1 | c.2558G>A | p.Ser853Asn | missense_variant | 13/13 | ||
MED1 | XM_047436315.1 | c.2417G>A | p.Ser806Asn | missense_variant | 9/9 | ||
MED1 | XM_006721957.3 | c.1640+1434G>A | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MED1 | ENST00000300651.11 | c.3074G>A | p.Ser1025Asn | missense_variant | 17/17 | 1 | NM_004774.4 | P1 | |
MED1 | ENST00000394287.7 | c.1640+1434G>A | intron_variant | 1 | |||||
MED1 | ENST00000577831.5 | c.*2647G>A | 3_prime_UTR_variant, NMD_transcript_variant | 16/16 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.000500 AC: 76AN: 152152Hom.: 0 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
76
AN:
152152
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.0000994 AC: 25AN: 251438Hom.: 0 AF XY: 0.0000662 AC XY: 9AN XY: 135888
GnomAD3 exomes
AF:
AC:
25
AN:
251438
Hom.:
AF XY:
AC XY:
9
AN XY:
135888
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000465 AC: 68AN: 1461888Hom.: 1 Cov.: 35 AF XY: 0.0000344 AC XY: 25AN XY: 727248
GnomAD4 exome
AF:
AC:
68
AN:
1461888
Hom.:
Cov.:
35
AF XY:
AC XY:
25
AN XY:
727248
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000493 AC: 75AN: 152270Hom.: 0 Cov.: 32 AF XY: 0.000483 AC XY: 36AN XY: 74468
GnomAD4 genome
?
AF:
AC:
75
AN:
152270
Hom.:
Cov.:
32
AF XY:
AC XY:
36
AN XY:
74468
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ESP6500AA
AF:
AC:
9
ESP6500EA
AF:
AC:
0
ExAC
?
AF:
AC:
20
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 | Feb 06, 2024 | The c.3074G>A (p.S1025N) alteration is located in exon 17 (coding exon 17) of the MED1 gene. This alteration results from a G to A substitution at nucleotide position 3074, causing the serine (S) at amino acid position 1025 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
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