NM_025205.5:c.253C>T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_025205.5(MED28):​c.253C>T​(p.Leu85Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,453,380 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: MED28 NM_025205.5 synonymous
• Clinical Significance: Not reported in ClinVar
• 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: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.33).
• BP7: Synonymous conserved (PhyloP=2.05 with no splicing effect.

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>T	p.Leu85Leu	synonymous	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>T	p.Leu85Leu	synonymous	Exon 3 of 4	ENSP00000237380.6	Q9H204
	MED28	ENST00000503945.2	TSL:1	n.244C>T		non_coding_transcript_exon	Exon 3 of 6	ENSP00000426529.1	H0YAA8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000138 AC: 2 AN: 1453380 Hom.: 0 Cov.: 30 AF XY: 0.00000139 AC XY: 1 AN XY: 721950

African (AFR) AF: 0.00 AC: 0 AN: 33186

American (AMR) AF: 0.00 AC: 0 AN: 43468

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26070

East Asian (EAS) AF: 0.0000506 AC: 2 AN: 39546

South Asian (SAS) AF: 0.00 AC: 0 AN: 82174

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53378

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1109624

Other (OTH) AF: 0.00 AC: 0 AN: 60182

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
CADD	Benign	9.3
DANN	Benign	0.76
PhyloP100		2.1

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;