18-60371474-CATG-C
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM1PM4_Supporting
The NM_005912.3(MC4R):c.873_875del(p.Ile291del) variant causes a inframe deletion change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000867 in 1,614,028 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000082 ( 0 hom. )
Consequence
MC4R
NM_005912.3 inframe_deletion
NM_005912.3 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
MC4R (HGNC:6932): (melanocortin 4 receptor) The protein encoded by this gene is a membrane-bound receptor and member of the melanocortin receptor family. The encoded protein interacts with adrenocorticotropic and MSH hormones and is mediated by G proteins. This is an intronless gene. Defects in this gene are a cause of autosomal dominant obesity. [provided by RefSeq, Jan 2010]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 3 ACMG points.
PM1
?
In a transmembrane_region Helical; Name=7 (size 23) in uniprot entity MC4R_HUMAN there are 7 pathogenic changes around while only 0 benign (100%) in NM_005912.3
PM4
?
Nonframeshift variant in NON repetitive region in NM_005912.3. Strenght limited to Supporting due to length of the change: 1aa.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MC4R | NM_005912.3 | c.873_875del | p.Ile291del | inframe_deletion | 1/1 | ENST00000299766.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MC4R | ENST00000299766.5 | c.873_875del | p.Ile291del | inframe_deletion | 1/1 | NM_005912.3 | P1 | ||
ENST00000658928.1 | n.156+42132_156+42134del | intron_variant, non_coding_transcript_variant | |||||||
ENST00000650201.1 | n.113+42132_113+42134del | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251386Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135860
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GnomAD4 exome AF: 0.00000821 AC: 12AN: 1461866Hom.: 0 AF XY: 0.0000110 AC XY: 8AN XY: 727236
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GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152162Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74314
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 27, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 1919464). This variant has been observed in individual(s) with features of MC4R-related conditions (PMID: 32952152). This variant is present in population databases (rs754899496, gnomAD 0.04%). This variant, c.873_875del, results in the deletion of 1 amino acid(s) of the MC4R protein (p.Ile291del), but otherwise preserves the integrity of the reading frame. - |
Computational scores
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at