Variant 4-17621689-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_025205.5(MED28):c.329T>G(p.Val110Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000809 in 1,607,222 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

MED28
NM_025205.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.72

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MED28	NM_025205.5 linkuse as main transcript	c.329T>G	p.Val110Gly	missense_variant	3/4	ENST00000237380.12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MED28	ENST00000237380.12 linkuse as main transcript	c.329T>G	p.Val110Gly	missense_variant	3/4	1	NM_025205.5	P1
MED28	ENST00000503945.2 linkuse as main transcript	c.320T>G	p.Val107Gly	missense_variant, NMD_transcript_variant	3/6	1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000609

AC:

AN:

246248

Hom.:

AF XY:

0.0000376

AC XY:

AN XY:

133044

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000829

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000619

AC:

AN:

1455042

Hom.:

Cov.:

AF XY:

0.00000415

AC XY:

AN XY:

723520

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000227

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152180

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000770

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000302

ExAC

AF:

0.0000577

AC:

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

Feb 27, 2024

The c.329T>G (p.V110G) alteration is located in exon 3 (coding exon 3) of the MED28 gene. This alteration results from a T to G substitution at nucleotide position 329, causing the valine (V) at amino acid position 110 to be replaced by a glycine (G). 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

Pathogenic

0.86

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Pathogenic

0.41

Cadd

Pathogenic

Dann

Uncertain

1.0

DEOGEN2

Uncertain

0.51

Eigen

Pathogenic

0.72

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.84

M_CAP

Benign

0.054

MetaRNN

Uncertain

0.53

MetaSVM

Uncertain

-0.20

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.70

PROVEAN

Pathogenic

-5.4

REVEL

Uncertain

0.49

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0020

Polyphen

1.0

Vest4

0.69

MutPred

0.16

Loss of stability (P = 0.0454);

MVP

0.87

MPC

0.16

ClinPred

0.62

GERP RS

5.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.87

gMVP

0.57

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.41

Details are displayed if max score is > 0.2

DS_DG_spliceai

0.41

Position offset: -1

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