1-24331440-G-A
Variant summary
Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2
The NM_198173.3(GRHL3):c.32G>A(p.Arg11Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000215 in 1,612,412 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_198173.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -9 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GRHL3 | NM_198173.3 | c.32G>A | p.Arg11Gln | missense_variant | 2/16 | ENST00000361548.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GRHL3 | ENST00000361548.9 | c.32G>A | p.Arg11Gln | missense_variant | 2/16 | 1 | NM_198173.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.000802 AC: 122AN: 152146Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000360 AC: 90AN: 249946Hom.: 0 AF XY: 0.000259 AC XY: 35AN XY: 135082
GnomAD4 exome AF: 0.000153 AC: 224AN: 1460148Hom.: 0 Cov.: 31 AF XY: 0.000128 AC XY: 93AN XY: 726352
GnomAD4 genome AF: 0.000808 AC: 123AN: 152264Hom.: 0 Cov.: 32 AF XY: 0.000887 AC XY: 66AN XY: 74444
ClinVar
Submissions by phenotype
Isolated cleft palate Pathogenic:1
Likely pathogenic, no assertion criteria provided | research | Orthodontics Department, Peking University School and Hospital of Stomatology | Mar 01, 2021 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jun 11, 2021 | The c.32G>A (p.R11Q) alteration is located in exon 2 (coding exon 2) of the GRHL3 gene. This alteration results from a G to A substitution at nucleotide position 32, causing the arginine (R) at amino acid position 11 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
GRHL3-related disorder Benign:1
Likely benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 20, 2019 | 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). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at