chr17-17477147-C-T

Variant names:

• chr17-17477147-C-T
• NM_018019.3:c.106C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018019.3(MED9):​c.106C>T​(p.Pro36Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,456,266 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: MED9 NM_018019.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.110

Genes affected

MED9 (HGNC:25487): (mediator complex subunit 9) The multiprotein Mediator complex is a coactivator required for activation of RNA polymerase II transcription by DNA bound transcription factors. The protein encoded by this gene is thought to be a subunit of the Mediator complex. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10423264).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MED9	NM_018019.3	c.106C>T	p.Pro36Ser	missense_variant	Exon 1 of 2	ENST00000268711.4	NP_060489.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MED9	ENST00000268711.4	c.106C>T	p.Pro36Ser	missense_variant	Exon 1 of 2	1	NM_018019.3	ENSP00000268711.3
MED9	ENST00000580462.1	c.106C>T	p.Pro36Ser	missense_variant	Exon 1 of 2	1		ENSP00000463031.1
MED9	ENST00000581315.1	n.106C>T		non_coding_transcript_exon_variant	Exon 1 of 3	4		ENSP00000462204.1
MED9	ENST00000585041.1	n.142C>T		non_coding_transcript_exon_variant	Exon 1 of 1	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456266 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 724070

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: 9.01e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 14, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.106C>T (p.P36S) alteration is located in exon 1 (coding exon 1) of the MED9 gene. This alteration results from a C to T substitution at nucleotide position 106, causing the proline (P) at amino acid position 36 to be replaced by a serine (S). 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	Benign	0.067
BayesDel_addAF	Benign	-0.083	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	18
DANN	Benign	0.97
DEOGEN2	Benign	0.068	T;T
Eigen	Benign	-0.52
Eigen_PC	Benign	-0.42
FATHMM_MKL	Benign	0.023	N
LIST_S2	Benign	0.58	T;.
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.10	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Benign	0.42	N;.
REVEL	Benign	0.097
Sift	Uncertain	0.019	D;.
Sift4G	Benign	0.44	T;T
Polyphen		0.19	B;.
Vest4		0.31
MutPred		0.24		Gain of phosphorylation at P36 (P = 0.0033);Gain of phosphorylation at P36 (P = 0.0033);
MVP		0.33
MPC		0.81
ClinPred		0.39	T
GERP RS		3.5
Varity_R		0.062
gMVP		0.33

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: chr17-17380461;