Genetic Variant NM_032849.4:c.191C>T (chr13-30906706-C-T) – 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.191C>T(p.Ala64Val) 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. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A64G) has been classified 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

Not reported in ClinVar

Conservation

PhyloP100: 0.0120

Publications

1 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=0.089387655).

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.191C>T	p.Ala64Val	missense	Exon 1 of 5	NP_116238.3
	TEX26-AS1	NR_038287.1		n.1438-22646G>A		intron	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
MEDAG	ENST00000380482.9	TSL:1 MANE Select	c.191C>T	p.Ala64Val	missense	Exon 1 of 5	ENSP00000369849.4	Q5VYS4-1
MEDAG	ENST00000904728.1		c.191C>T	p.Ala64Val	missense	Exon 1 of 5	ENSP00000574787.1
MEDAG	ENST00000968515.1		c.191C>T	p.Ala64Val	missense	Exon 1 of 3	ENSP00000638574.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1366448

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

674142

African (AFR)

AF:

0.00

AC:

AN:

29482

American (AMR)

AF:

0.00

AC:

AN:

32988

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23130

East Asian (EAS)

AF:

0.00

AC:

AN:

35334

South Asian (SAS)

AF:

0.00

AC:

AN:

75252

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34204

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4982

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1074172

Other (OTH)

AF:

0.00

AC:

AN:

56904

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.011

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.92

FATHMM_MKL

Benign

0.019

LIST_S2

Benign

0.46

M_CAP

Benign

0.019

MetaRNN

Benign

0.089

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

0.012

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-1.6

REVEL

Benign

0.038

Sift

Benign

0.056

Sift4G

Pathogenic

0.0

Polyphen

0.011

Vest4

0.085

MutPred

0.63

Gain of sheet (P = 0.0166)

MVP

0.11

MPC

0.12

ClinPred

0.098

GERP RS

-0.35

PromoterAI

-0.044

Neutral

(source)

Varity_R

0.067

gMVP

0.28

Mutation Taster

=92/8

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