rs1714634344

Variant names:

• chr4-17621613-C-G
• rs1714634344
• NM_025205.5:c.253C>G

Your query was ambiguous. Multiple possible variants found:

• chr4-17621613-C-G
• chr4-17621613-C-T

Variant summary

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

The NM_025205.5(MED28):​c.253C>G​(p.Leu85Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: MED28 NM_025205.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.05
• Publications: 0 publications found

Genes affected

MED28 (HGNC:24628): (mediator complex subunit 28) Predicted to enable actin binding activity. Predicted to act upstream of or within negative regulation of smooth muscle cell differentiation and stem cell population maintenance. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025205.5. 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
	MED28	NM_025205.5	MANE Select	c.253C>G	p.Leu85Val	missense	Exon 3 of 4	NP_079481.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MED28	ENST00000237380.12	TSL:1 MANE Select	c.253C>G	p.Leu85Val	missense	Exon 3 of 4	ENSP00000237380.6	Q9H204
	MED28	ENST00000503945.2	TSL:1	n.244C>G		non_coding_transcript_exon	Exon 3 of 6	ENSP00000426529.1	H0YAA8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.84
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.23
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.35
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.012	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.58	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.1
PrimateAI	Uncertain	0.75	T
PROVEAN	Benign	-0.90	N
REVEL	Benign	0.23
Sift	Uncertain	0.017	D
Sift4G	Uncertain	0.038	D
Polyphen		1.0	D
Vest4		0.68
MutPred		0.34		Gain of methylation at K83 (P = 0.1511)
MVP		0.51
MPC		0.041
ClinPred		0.73	D
GERP RS		2.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.17
gMVP		0.45
Mutation Taster		=76/24	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: rs1714634344; hg19: chr4-17623236;