chr11-93784720-G-T

Variant names:

• chr11-93784720-G-T
• rs2848477
• NM_004268.5:c.207G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004268.5(MED17):​c.207G>T​(p.Glu69Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: MED17 NM_004268.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.209
• Publications: 33 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]

MED17 Gene-Disease associations (from GenCC):

• infantile cerebral and cerebellar atrophy with postnatal progressive microcephaly

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Orphanet

ENSG00000284057 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.113281876).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED17	NM_004268.5	MANE Select	c.207G>T	p.Glu69Asp	missense	Exon 1 of 12	NP_004259.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED17	ENST00000251871.9	TSL:1 MANE Select	c.207G>T	p.Glu69Asp	missense	Exon 1 of 12	ENSP00000251871.3
	ENSG00000284057	ENST00000638767.1	TSL:5	c.768G>T	p.Glu256Asp	missense	Exon 8 of 19	ENSP00000492220.1
	MED17	ENST00000639724.1	TSL:5	c.207G>T	p.Glu69Asp	missense	Exon 1 of 11	ENSP00000492625.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000665 AC: 1 AN: 150320 AF XY: 0.0000124

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000853

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 7.17e-7 AC: 1 AN: 1394548 Hom.: 0 Cov.: 76 AF XY: 0.00000145 AC XY: 1 AN XY: 688308

African (AFR) AF: 0.00 AC: 0 AN: 32106

American (AMR) AF: 0.00 AC: 0 AN: 35740

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.0000275 AC: 1 AN: 36410

South Asian (SAS) AF: 0.00 AC: 0 AN: 79532

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41422

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5350

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1080742

Other (OTH) AF: 0.00 AC: 0 AN: 58078

GnomAD4 genome Cov.: 33

ExAC AF: 0.0000109 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.054
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.56
CADD	Benign	10
DANN	Benign	0.71
DEOGEN2	Benign	0.054	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.61	D
LIST_S2	Benign	0.22	T
M_CAP	Benign	0.055	D
MetaRNN	Benign	0.11	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.4	L
PhyloP100		0.21
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.20	N
REVEL	Benign	0.15
Sift	Benign	0.87	T
Sift4G	Benign	0.44	T
Polyphen		0.0	B
Vest4		0.018
MutPred		0.40		Gain of helix (P = 0.027)
MVP		0.36
MPC		0.25
ClinPred		0.041	T
GERP RS		1.7
PromoterAI		0.085	Neutral
Varity_R		0.075
gMVP		0.24
Mutation Taster		=88/12	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: rs2848477; hg19: chr11-93517886;