rs753181516
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_003737.4(DCHS1):c.9791G>A(p.Arg3264His) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,612,014 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003737.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000812 AC: 2AN: 246346Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 133442
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1459824Hom.: 0 Cov.: 31 AF XY: 0.0000124 AC XY: 9AN XY: 725916
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74352
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.9791G>A (p.R3264H) alteration is located in exon 21 (coding exon 20) of the DCHS1 gene. This alteration results from a G to A substitution at nucleotide position 9791, causing the arginine (R) at amino acid position 3264 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
not provided Uncertain:1
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 3264 of the DCHS1 protein (p.Arg3264His). This variant is present in population databases (rs753181516, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with DCHS1-related conditions. 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 DCHS1 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