Variant 13-30921809-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_032849.4(MEDAG):c.750C>A(p.Ser250Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000466 in 1,610,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00028 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000023 ( 0 hom. )

Consequence

MEDAG
NM_032849.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.57

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 made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11539653).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
MEDAG	NM_032849.4 linkuse as main transcript	c.750C>A	p.Ser250Arg	missense_variant	4/5	ENST00000380482.9	NP_116238.3
TEX26-AS1	NR_038287.1 linkuse as main transcript	n.1437+8992G>T		intron_variant, non_coding_transcript_variant
MEDAG	XM_017020801.2 linkuse as main transcript	c.297C>A	p.Ser99Arg	missense_variant	3/4		XP_016876290.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MEDAG	ENST00000380482.9 linkuse as main transcript	c.750C>A	p.Ser250Arg	missense_variant	4/5	1	NM_032849.4	ENSP00000369849	P1	Q5VYS4-1
TEX26-AS1	ENST00000585870.6 linkuse as main transcript	n.1437+8992G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.000276

AC:

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.0000363

AC:

AN:

247668

Hom.:

AF XY:

0.0000299

AC XY:

AN XY:

133884

show subpopulations

Gnomad AFR exome

AF:

0.000498

Gnomad AMR exome

AF:

0.0000295

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

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:

0.0000226

AC:

AN:

1458234

Hom.:

Cov.:

AF XY:

0.0000110

AC XY:

AN XY:

725182

show subpopulations

Gnomad4 AFR exome

AF:

0.000785

Gnomad4 AMR exome

AF:

0.0000910

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:

0.00

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.000276

AC:

AN:

152298

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000890

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000132

Hom.:

Bravo

AF:

0.000325

ExAC

AF:

0.0000412

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

Aug 13, 2021

The c.750C>A (p.S250R) alteration is located in exon 4 (coding exon 4) of the MEDAG gene. This alteration results from a C to A substitution at nucleotide position 750, causing the serine (S) at amino acid position 250 to be replaced by an arginine (R). 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

0.91

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.24

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.76

M_CAP

Benign

0.012

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.81

MutationAssessor

Benign

0.69

MutationTaster

Benign

0.69

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-2.3

REVEL

Benign

0.14

Sift

Uncertain

0.019

Sift4G

Benign

0.092

Polyphen

0.95

Vest4

0.51

MutPred

0.26

Loss of phosphorylation at S250 (P = 0.0055);

MVP

0.34

MPC

0.31

ClinPred

0.10

GERP RS

4.5

Varity_R

0.17

gMVP

0.43

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