Variant 13-30921020-C-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000380482.9(MEDAG):c.395C>A(p.Thr132Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,460,734 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. T132T) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

MEDAG
ENST00000380482.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.15

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 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	Protein
MEDAG	NM_032849.4 linkuse as main transcript	c.395C>A	p.Thr132Lys	missense_variant	3/5	ENST00000380482.9	NP_116238.3
TEX26-AS1	NR_038287.1 linkuse as main transcript	n.1437+9781G>T		intron_variant, non_coding_transcript_variant
MEDAG	XM_017020801.2 linkuse as main transcript	c.-59C>A		5_prime_UTR_variant	2/4		XP_016876290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEDAG	ENST00000380482.9 linkuse as main transcript	c.395C>A	p.Thr132Lys	missense_variant	3/5	1	NM_032849.4	ENSP00000369849	P1	Q5VYS4-1
TEX26-AS1	ENST00000585870.6 linkuse as main transcript	n.1437+9781G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1460734

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726578

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:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000594

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

Dec 20, 2023

The c.395C>A (p.T132K) alteration is located in exon 3 (coding exon 3) of the MEDAG gene. This alteration results from a C to A substitution at nucleotide position 395, causing the threonine (T) at amino acid position 132 to be replaced by a lysine (K). 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

0.92

BayesDel_addAF

Pathogenic

0.18

BayesDel_noAF

Uncertain

0.020

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.19

Eigen

Uncertain

0.45

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.74

M_CAP

Benign

0.0079

MetaRNN

Uncertain

0.62

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.97

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.63

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.27

Sift

Benign

0.052

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.75

MutPred

0.45

Loss of sheet (P = 0.0228);

MVP

0.42

MPC

0.62

ClinPred

0.91

GERP RS

5.3

Varity_R

0.22

gMVP

0.63

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