chr11-93784518-C-G

Variant names:

• chr11-93784518-C-G
• rs201799308
• NM_004268.5:c.5C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004268.5(MED17):​c.5C>G​(p.Ser2Cys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S2F) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: MED17 NM_004268.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.12
• Publications: 0 publications found

Genes affected

MED17 (HGNC:2375): (mediator complex subunit 17) 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. [provided by RefSeq, Jul 2008]

ENSG00000284057 (HGNC:):

TAF1D (HGNC:28759): (TATA-box binding protein associated factor, RNA polymerase I subunit D) TAF1D is a member of the SL1 complex, which includes TBP (MIM 600075) and TAF1A (MIM 604903), TAF1B (MIM 604904), and TAF1C (MIM 604905), and plays a role in RNA polymerase I transcription (Wang et al., 2004 [PubMed 15520167]; Gorski et al., 2007 [PubMed 17318177]).[supplied by OMIM, Jun 2009]

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.40684512).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004268.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED17	NM_004268.5	MANE Select	c.5C>G	p.Ser2Cys	missense	Exon 1 of 12	NP_004259.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED17	ENST00000251871.9	TSL:1 MANE Select	c.5C>G	p.Ser2Cys	missense	Exon 1 of 12	ENSP00000251871.3	Q9NVC6-1
	ENSG00000284057	ENST00000638767.1	TSL:5	c.676-110C>G		intron	N/A	ENSP00000492220.1	A0A1W2PRB8
	MED17	ENST00000639724.1	TSL:5	c.5C>G	p.Ser2Cys	missense	Exon 1 of 11	ENSP00000492625.1	A0A1W2PS27

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.28
BayesDel_addAF	Uncertain	0.024	T
BayesDel_noAF	Benign	-0.20
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.57
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.86	D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.41	T
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	1.7	L
PhyloP100		7.1
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.013	D
Polyphen		0.38	B
Vest4		0.45
MutPred		0.40		Loss of disorder (P = 0.0041)
MVP		0.82
MPC		0.52
ClinPred		0.98	D
GERP RS		5.8
PromoterAI		-0.17	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.20
gMVP		0.83
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs201799308; hg19: chr11-93517684;