rs45588036
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM1BP4
The NM_000163.5(GHR):āc.726G>Cā(p.Glu242Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,613,036 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 (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E242K) has been classified as Uncertain significance.
Frequency
Consequence
NM_000163.5 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GHR | NM_000163.5 | c.726G>C | p.Glu242Asp | missense_variant | 7/10 | ENST00000230882.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GHR | ENST00000230882.9 | c.726G>C | p.Glu242Asp | missense_variant | 7/10 | 1 | NM_000163.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152152Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000199 AC: 5AN: 251374Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135854
GnomAD4 exome AF: 0.0000589 AC: 86AN: 1460884Hom.: 0 Cov.: 30 AF XY: 0.0000592 AC XY: 43AN XY: 726832
GnomAD4 genome ? AF: 0.0000526 AC: 8AN: 152152Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74326
ClinVar
Submissions by phenotype
Short stature due to partial GHR deficiency Pathogenic:1Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Institute of Human Genetics, University of Leipzig Medical Center | May 17, 2022 | Criteria applied: PS4_SUP - |
Pathogenic, no assertion criteria provided | literature only | OMIM | Oct 26, 1995 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 01, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 242 of the GHR protein (p.Glu242Asp). This variant is present in population databases (rs45588036, gnomAD 0.008%). This missense change has been observed in individual(s) with growth hormone insensitivity (PMID: 7565946). This variant is also known as p.Glu224Asp. ClinVar contains an entry for this variant (Variation ID: 8638). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35". The aspartic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at