19-49830209-G-C

Position:

• chr19-49830209-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_030973.4(MED25):​c.810G>C​(p.Pro270Pro) variant causes a synonymous 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. 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 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.223

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 Likely_benign. Variant got -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP7: Synonymous conserved (PhyloP=0.223 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED25	NM_030973.4	c.810G>C	p.Pro270Pro	synonymous_variant	7/18	ENST00000312865.10	NP_112235.2
MED25	NM_001378355.1	c.810G>C	p.Pro270Pro	synonymous_variant	7/18		NP_001365284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED25	ENST00000312865.10	c.810G>C	p.Pro270Pro	synonymous_variant	7/18	1	NM_030973.4	ENSP00000326767.5
MED25	ENST00000538643.5	c.181-302G>C		intron_variant		1		ENSP00000437496.1
MED25	ENST00000595185.5	c.688+261G>C		intron_variant		1		ENSP00000470027.1
MED25	ENST00000593767.3	c.810G>C	p.Pro270Pro	synonymous_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
BayesDel_noAF	Benign	-0.54
CADD	Benign	3.8
DANN	Benign	0.44

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: chr19-50333466;