Genetic Variant MEDAG:p.Thr139Thr (chr13-30921042-G-A) – ACMG Classification: Benign (-9 pts)

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7BA1

The NM_032849.4(MEDAG):c.417G>A(p.Thr139Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0913 in 1,613,350 control chromosomes in the GnomAD database, including 7,679 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1301 hom., cov: 33)

Exomes 𝑓: 0.088 ( 6378 hom. )

Consequence

MEDAG
NM_032849.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.133

Publications

11 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -9 ACMG points.

BP7

Synonymous conserved (PhyloP=-0.133 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MEDAG	NM_032849.4 link	c.417G>A	p.Thr139Thr	synonymous_variant	Exon 3 of 5	ENST00000380482.9	NP_116238.3	Q5VYS4-1
MEDAG	XM_017020801.2 link	c.-37G>A		5_prime_UTR_variant	Exon 2 of 4		XP_016876290.1
TEX26-AS1	NR_038287.1 link	n.1437+9759C>T		intron_variant	Intron 2 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MEDAG	ENST00000380482.9 link	c.417G>A	p.Thr139Thr	synonymous_variant	Exon 3 of 5	1	NM_032849.4	ENSP00000369849.4		Q5VYS4-1

Frequencies

GnomAD3 genomes

AF:

0.118

AC:

17912

AN:

152052

Hom.:

1289

Cov.:

show subpopulations

Gnomad AFR

AF:

0.199

Gnomad AMI

AF:

0.0637

Gnomad AMR

AF:

0.112

Gnomad ASJ

AF:

0.0346

Gnomad EAS

AF:

0.0163

Gnomad SAS

AF:

0.0576

Gnomad FIN

AF:

0.128

Gnomad MID

AF:

0.0570

Gnomad NFE

AF:

0.0858

Gnomad OTH

AF:

0.100

GnomAD2 exomes

AF:

0.0902

AC:

22646

AN:

251104

AF XY:

0.0860

show subpopulations

Gnomad AFR exome

AF:

0.201

Gnomad AMR exome

AF:

0.115

Gnomad ASJ exome

AF:

0.0342

Gnomad EAS exome

AF:

0.0185

Gnomad FIN exome

AF:

0.123

Gnomad NFE exome

AF:

0.0857

Gnomad OTH exome

AF:

0.0819

GnomAD4 exome

AF:

0.0885

AC:

129313

AN:

1461180

Hom.:

6378

Cov.:

AF XY:

0.0865

AC XY:

62870

AN XY:

726902

show subpopulations

African (AFR)

AF:

0.200

AC:

6707

AN:

33462

American (AMR)

AF:

0.116

AC:

5174

AN:

44696

Ashkenazi Jewish (ASJ)

AF:

0.0350

AC:

914

AN:

26132

East Asian (EAS)

AF:

0.0153

AC:

608

AN:

39700

South Asian (SAS)

AF:

0.0597

AC:

5149

AN:

86194

European-Finnish (FIN)

AF:

0.123

AC:

6543

AN:

53408

Middle Eastern (MID)

AF:

0.0584

AC:

337

AN:

5766

European-Non Finnish (NFE)

AF:

0.0889

AC:

98793

AN:

1111446

Other (OTH)

AF:

0.0843

AC:

5088

AN:

60376

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

5739

11479

17218

22958

28697

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3766

7532

11298

15064

18830

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.118

AC:

17962

AN:

152170

Hom.:

1301

Cov.:

AF XY:

0.118

AC XY:

8767

AN XY:

74404

show subpopulations

African (AFR)

AF:

0.200

AC:

8293

AN:

41492

American (AMR)

AF:

0.112

AC:

1706

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.0346

AC:

120

AN:

3468

East Asian (EAS)

AF:

0.0164

AC:

AN:

5188

South Asian (SAS)

AF:

0.0577

AC:

278

AN:

4822

European-Finnish (FIN)

AF:

0.128

AC:

1353

AN:

10574

Middle Eastern (MID)

AF:

0.0578

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0858

AC:

5838

AN:

68024

Other (OTH)

AF:

0.101

AC:

214

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

835

1671

2506

3342

4177

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

188

376

564

752

940

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0900

Hom.:

1665

Bravo

AF:

0.120

Asia WGS

AF:

0.0590

AC:

207

AN:

3478

EpiCase

AF:

0.0790

EpiControl

AF:

0.0809

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

6.4

(source)

DANN

Benign

0.66

PhyloP100

-0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over