rs80326661
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_000939.4(POMC):c.641A>G(p.Glu214Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00679 in 1,611,820 control chromosomes in the GnomAD database, including 45 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. E214E) has been classified as Uncertain significance.
Frequency
Consequence
NM_000939.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
POMC | NM_000939.4 | c.641A>G | p.Glu214Gly | missense_variant | 3/3 | ENST00000395826.7 | |
POMC | NM_001035256.3 | c.641A>G | p.Glu214Gly | missense_variant | 4/4 | ||
POMC | NM_001319204.2 | c.641A>G | p.Glu214Gly | missense_variant | 4/4 | ||
POMC | NM_001319205.2 | c.641A>G | p.Glu214Gly | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
POMC | ENST00000395826.7 | c.641A>G | p.Glu214Gly | missense_variant | 3/3 | 2 | NM_000939.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00524 AC: 793AN: 151424Hom.: 7 Cov.: 33
GnomAD3 exomes AF: 0.00542 AC: 1348AN: 248690Hom.: 5 AF XY: 0.00542 AC XY: 730AN XY: 134752
GnomAD4 exome AF: 0.00695 AC: 10154AN: 1460276Hom.: 38 Cov.: 32 AF XY: 0.00683 AC XY: 4960AN XY: 726312
GnomAD4 genome ? AF: 0.00523 AC: 793AN: 151544Hom.: 7 Cov.: 33 AF XY: 0.00478 AC XY: 354AN XY: 74076
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Nov 01, 2023 | POMC: BS2 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 25, 2019 | - - |
POMC-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 21, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Obesity Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at