13-30921745-C-T

Variant summary

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

The NM_032849.4(MEDAG):​c.686C>T​(p.Pro229Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000124 in 1,613,906 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

MEDAG
NM_032849.4 missense

Scores

1
7
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.04
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]
TEX26-AS1 (HGNC:42784): (TEX26 antisense RNA 1)

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=0.20300964).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
MEDAGNM_032849.4 linkuse as main transcriptc.686C>T p.Pro229Leu missense_variant 4/5 ENST00000380482.9 NP_116238.3
TEX26-AS1NR_038287.1 linkuse as main transcriptn.1437+9056G>A intron_variant, non_coding_transcript_variant
MEDAGXM_017020801.2 linkuse as main transcriptc.233C>T p.Pro78Leu missense_variant 3/4 XP_016876290.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
MEDAGENST00000380482.9 linkuse as main transcriptc.686C>T p.Pro229Leu missense_variant 4/51 NM_032849.4 ENSP00000369849 P1Q5VYS4-1
TEX26-AS1ENST00000585870.6 linkuse as main transcriptn.1437+9056G>A intron_variant, non_coding_transcript_variant 2

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152160
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000797
AC:
2
AN:
251054
Hom.:
0
AF XY:
0.0000147
AC XY:
2
AN XY:
135694
show subpopulations
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 SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461628
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727090
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:
0.00
Gnomad4 OTH exome
AF:
0.0000166
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152278
Hom.:
0
Cov.:
32
AF XY:
0.0000134
AC XY:
1
AN XY:
74458
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000111
Hom.:
0
ExAC
AF:
0.00000824
AC:
1

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 submitterclinical testingAmbry GeneticsNov 29, 2023The c.686C>T (p.P229L) alteration is located in exon 4 (coding exon 4) of the MEDAG gene. This alteration results from a C to T substitution at nucleotide position 686, causing the proline (P) at amino acid position 229 to be replaced by a leucine (L). 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
Benign
0.14
BayesDel_addAF
Benign
-0.084
T
BayesDel_noAF
Benign
-0.36
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.19
T
Eigen
Uncertain
0.39
Eigen_PC
Uncertain
0.45
FATHMM_MKL
Uncertain
0.83
D
LIST_S2
Benign
0.84
T
M_CAP
Benign
0.0090
T
MetaRNN
Benign
0.20
T
MetaSVM
Benign
-0.94
T
MutationAssessor
Benign
0.81
L
MutationTaster
Benign
1.0
D
PrimateAI
Uncertain
0.55
T
PROVEAN
Pathogenic
-5.3
D
REVEL
Benign
0.16
Sift
Uncertain
0.0030
D
Sift4G
Uncertain
0.0080
D
Polyphen
0.94
P
Vest4
0.42
MutPred
0.49
Loss of ubiquitination at K232 (P = 0.0345);
MVP
0.34
MPC
0.26
ClinPred
0.86
D
GERP RS
5.2
Varity_R
0.24
gMVP
0.39

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs576074999; hg19: chr13-31495882; API