Genetic Variant NM_032849.4:c.225C>A (chr13-30906740-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032849.4(MEDAG):c.225C>A(p.Asp75Glu) variant causes a missense 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. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

MEDAG
NM_032849.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.297

Publications

0 publications found

Variant links:

Genes affected

MEDAG (HGNC:25926): (mesenteric estrogen dependent adipogenesis) Predicted to be involved in positive regulation of fat cell differentiation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MEDAG links:

TEX26-AS1 (HGNC:42784): (TEX26 antisense RNA 1)

TEX26-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.2630164).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032849.4. 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
	MEDAG	NM_032849.4	MANE Select	c.225C>A	p.Asp75Glu	missense	Exon 1 of 5	NP_116238.3
	TEX26-AS1	NR_038287.1		n.1438-22680G>T		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEDAG	ENST00000380482.9	TSL:1 MANE Select	c.225C>A	p.Asp75Glu	missense	Exon 1 of 5	ENSP00000369849.4	Q5VYS4-1
MEDAG	ENST00000904728.1		c.225C>A	p.Asp75Glu	missense	Exon 1 of 5	ENSP00000574787.1
MEDAG	ENST00000968515.1		c.225C>A	p.Asp75Glu	missense	Exon 1 of 3	ENSP00000638574.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

118770

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1358526

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

670704

African (AFR)

AF:

0.00

AC:

AN:

28508

American (AMR)

AF:

0.00

AC:

AN:

32654

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22528

East Asian (EAS)

AF:

0.00

AC:

AN:

34044

South Asian (SAS)

AF:

0.00

AC:

AN:

73964

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5012

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1071150

Other (OTH)

AF:

0.00

AC:

AN:

56530

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000873

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.16

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.32

LIST_S2

Benign

0.60

M_CAP

Benign

0.077

MetaRNN

Benign

0.26

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.81

PhyloP100

-0.30

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.098

Sift

Uncertain

0.0090

Sift4G

Benign

0.062

Polyphen

0.83

Vest4

0.36

MutPred

0.55

Gain of sheet (P = 0.0266)

MVP

0.50

MPC

0.18

ClinPred

0.98

GERP RS

2.1

PromoterAI

-0.031

Neutral

(source)

Varity_R

0.29

gMVP

0.63

Mutation Taster

=84/16

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over