2-25161259-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_000939.4(POMC):c.626T>C(p.Leu209Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000285 in 1,611,720 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_000939.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMC | NM_000939.4 | c.626T>C | p.Leu209Pro | missense_variant | 3/3 | ENST00000395826.7 | |
POMC | NM_001035256.3 | c.626T>C | p.Leu209Pro | missense_variant | 4/4 | ||
POMC | NM_001319204.2 | c.626T>C | p.Leu209Pro | missense_variant | 4/4 | ||
POMC | NM_001319205.2 | c.626T>C | p.Leu209Pro | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMC | ENST00000395826.7 | c.626T>C | p.Leu209Pro | missense_variant | 3/3 | 2 | NM_000939.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000726 AC: 11AN: 151536Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000566 AC: 14AN: 247542Hom.: 1 AF XY: 0.0000670 AC XY: 9AN XY: 134316
GnomAD4 exome AF: 0.0000240 AC: 35AN: 1460184Hom.: 1 Cov.: 32 AF XY: 0.0000289 AC XY: 21AN XY: 726226
GnomAD4 genome ? AF: 0.0000726 AC: 11AN: 151536Hom.: 0 Cov.: 33 AF XY: 0.0000811 AC XY: 6AN XY: 73998
ClinVar
Submissions by phenotype
POMC-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 20, 2023 | The POMC c.626T>C variant is predicted to result in the amino acid substitution p.Leu209Pro. This variant has been reported in individuals with an obesity phenotype (Table 3, Courbage et al. 2021. PubMed ID: 34097736; Dubern et al. 2008. PubMed ID: 18091355; Supplemental Data Set, Shah et al. 2023. PubMed ID: 36864747). This variant is reported in 0.023% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-25384128-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at