rs397514699
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_032551.5(KISS1R):c.581C>A(p.Ala194Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000516 in 1,570,040 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_032551.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KISS1R | NM_032551.5 | c.581C>A | p.Ala194Asp | missense_variant | 4/5 | ENST00000234371.10 | |
KISS1R | XM_047439545.1 | c.581C>A | p.Ala194Asp | missense_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KISS1R | ENST00000234371.10 | c.581C>A | p.Ala194Asp | missense_variant | 4/5 | 1 | NM_032551.5 | P1 | |
KISS1R | ENST00000606939.2 | c.505+324C>A | intron_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000855 AC: 13AN: 152108Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000347 AC: 6AN: 173152Hom.: 0 AF XY: 0.0000418 AC XY: 4AN XY: 95734
GnomAD4 exome AF: 0.0000480 AC: 68AN: 1417932Hom.: 0 Cov.: 33 AF XY: 0.0000512 AC XY: 36AN XY: 702654
GnomAD4 genome ? AF: 0.0000855 AC: 13AN: 152108Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74332
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 27, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 194 of the KISS1R protein (p.Ala194Asp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with hypogonadotropic hypogonadism (PMID: 23643382). ClinVar contains an entry for this variant (Variation ID: 50861). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KISS1R protein function with a negative predictive value of 80%. 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. - |
Hypogonadotropic hypogonadism 8 with or without anosmia Other:1
risk factor, no assertion criteria provided | literature only | OMIM | May 02, 2013 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at