13-30921745-C-T
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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
NM_032849.4 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 3.04
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]
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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 |
---|---|---|---|---|---|---|---|---|
MEDAG | NM_032849.4 | c.686C>T | p.Pro229Leu | missense_variant | 4/5 | ENST00000380482.9 | NP_116238.3 | |
TEX26-AS1 | NR_038287.1 | n.1437+9056G>A | intron_variant, non_coding_transcript_variant | |||||
MEDAG | XM_017020801.2 | c.233C>T | p.Pro78Leu | missense_variant | 3/4 | XP_016876290.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MEDAG | ENST00000380482.9 | c.686C>T | p.Pro229Leu | missense_variant | 4/5 | 1 | NM_032849.4 | ENSP00000369849 | P1 | |
TEX26-AS1 | ENST00000585870.6 | n.1437+9056G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152160Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000797 AC: 2AN: 251054Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135694
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GnomAD4 exome AF: 6.84e-7 AC: 1AN: 1461628Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1AN XY: 727090
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GnomAD4 genome AF: 0.00000657 AC: 1AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74458
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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 | Nov 29, 2023 | The 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MutPred
Loss of ubiquitination at K232 (P = 0.0345);
MVP
MPC
ClinPred
D
GERP RS
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gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at