rs779682957
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BS1_Supporting
The NM_021044.4(DHH):c.80G>A(p.Arg27Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000879 in 1,603,796 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_021044.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152202Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000143 AC: 31AN: 217350Hom.: 0 AF XY: 0.000207 AC XY: 25AN XY: 120502
GnomAD4 exome AF: 0.0000923 AC: 134AN: 1451476Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 87AN XY: 721400
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74482
ClinVar
Submissions by phenotype
46,XY sex reversal 7 Uncertain:1
This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 27 of the DHH protein (p.Arg27Gln). This variant is present in population databases (rs779682957, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with DHH-related conditions. ClinVar contains an entry for this variant (Variation ID: 466304). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DHH 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