5-42711312-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 4P and 2B. PM1PM5BP4_Moderate
The NM_000163.5(GHR):c.724G>A(p.Glu242Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000657 in 1,612,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E242D) has been classified as Uncertain significance.
Frequency
Consequence
NM_000163.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GHR | NM_000163.5 | c.724G>A | p.Glu242Lys | missense_variant | 7/10 | ENST00000230882.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GHR | ENST00000230882.9 | c.724G>A | p.Glu242Lys | missense_variant | 7/10 | 1 | NM_000163.5 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000131 AC: 20AN: 152124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000477 AC: 12AN: 251370Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135854
GnomAD4 exome AF: 0.0000589 AC: 86AN: 1460836Hom.: 0 Cov.: 30 AF XY: 0.0000592 AC XY: 43AN XY: 726814
GnomAD4 genome AF: 0.000131 AC: 20AN: 152124Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74312
ClinVar
Submissions by phenotype
Laron-type isolated somatotropin defect Uncertain:1
Uncertain significance, 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. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 28, 2022 | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 242 of the GHR protein (p.Glu242Lys). This variant is present in population databases (rs121909364, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with GHR-related conditions. ClinVar contains an entry for this variant (Variation ID: 907708). 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 C55". The lysine 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