Variant 4-17621601-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000237380.12(MED28):c.241A>G(p.Ile81Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000413 in 1,451,116 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I81T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MED28
ENST00000237380.12 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.17

Variant links:

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]

MED28 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.15678379).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MED28	NM_025205.5 linkuse as main transcript	c.241A>G	p.Ile81Val	missense_variant	3/4	ENST00000237380.12	NP_079481.2	Q9H204

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MED28	ENST00000237380.12 linkuse as main transcript	c.241A>G	p.Ile81Val	missense_variant	3/4	1	NM_025205.5	ENSP00000237380.6		Q9H204
MED28	ENST00000503945.2 linkuse as main transcript	n.232A>G		non_coding_transcript_exon_variant	3/6	1		ENSP00000426529.1		H0YAA8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000413

AC:

AN:

1451116

Hom.:

Cov.:

AF XY:

0.00000416

AC XY:

AN XY:

720748

show subpopulations

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:

0.00000451

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 02, 2023

The c.241A>G (p.I81V) alteration is located in exon 3 (coding exon 3) of the MED28 gene. This alteration results from a A to G substitution at nucleotide position 241, causing the isoleucine (I) at amino acid position 81 to be replaced by a valine (V). 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

0.19

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.12

Eigen

Benign

-0.15

Eigen_PC

Benign

0.0075

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.80

M_CAP

Benign

0.0075

MetaRNN

Benign

0.16

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Benign

0.030

REVEL

Benign

0.076

Sift

Benign

0.18

Sift4G

Benign

0.41

Polyphen

0.0010

Vest4

0.28

MutPred

0.22

Loss of methylation at K83 (P = 0.1084);

MVP

0.43

MPC

0.035

ClinPred

0.85

GERP RS

3.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.065

gMVP

0.21

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over