19-49830201-G-C

Position:

• chr19-49830201-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_030973.4(MED25):​c.802G>C​(p.Val268Leu) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: MED25 NM_030973.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.85

Genes affected

MED25 (HGNC:28845): (mediator complex subunit 25) This gene encodes a component of the transcriptional coactivator complex termed the Mediator complex. This complex is required for transcription of most RNA polymerase II-dependent genes. The encoded protein plays a role in chromatin modification and in preinitiation complex assembly. Mutations in this gene are associated with Charcot-Marie-Tooth disease type 2B2. [provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32934558).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED25	NM_030973.4	c.802G>C	p.Val268Leu	missense_variant	7/18	ENST00000312865.10	NP_112235.2
MED25	NM_001378355.1	c.802G>C	p.Val268Leu	missense_variant	7/18		NP_001365284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED25	ENST00000312865.10	c.802G>C	p.Val268Leu	missense_variant	7/18	1	NM_030973.4	ENSP00000326767.5
MED25	ENST00000538643.5	c.181-310G>C		intron_variant		1		ENSP00000437496.1
MED25	ENST00000595185.5	c.688+253G>C		intron_variant		1		ENSP00000470027.1
MED25	ENST00000593767.3	c.802G>C	p.Val268Leu	missense_variant	7/18	3		ENSP00000470692.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.13
BayesDel_addAF	Uncertain	0.056	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	.;T
Eigen	Benign	0.16
Eigen_PC	Benign	0.075
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Benign	0.73	T;T
M_CAP	Uncertain	0.18	D
MetaRNN	Benign	0.33	T;T
MetaSVM	Uncertain	-0.013	T
MutationAssessor	Benign	0.81	.;L
PrimateAI	Pathogenic	0.82	D
PROVEAN	Benign	-0.73	.;N
REVEL	Benign	0.27
Sift	Benign	0.033	.;D
Sift4G	Benign	0.19	T;T
Polyphen		1.0	.;D
Vest4		0.41
MutPred		0.11		Gain of catalytic residue at V268 (P = 0.0774);Gain of catalytic residue at V268 (P = 0.0774);
MVP		0.77
MPC		1.1
ClinPred		0.71	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.16
gMVP		0.26

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.11		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: chr19-50333458;