chr7-726789-G-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting
The NM_017802.4(DNAAF5):c.69G>T(p.Glu23Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000177 in 1,283,428 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/19 in silico tools predict 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. E23Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_017802.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DNAAF5 | NM_017802.4 | c.69G>T | p.Glu23Asp | missense_variant | 1/13 | ENST00000297440.11 | |
PRKAR1B | NM_001164760.2 | c.-23+421C>A | intron_variant | ENST00000537384.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF5 | ENST00000297440.11 | c.69G>T | p.Glu23Asp | missense_variant | 1/13 | 1 | NM_017802.4 | P1 | |
PRKAR1B | ENST00000537384.6 | c.-23+421C>A | intron_variant | 5 | NM_001164760.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000724 AC: 11AN: 151984Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000243 AC: 1AN: 4114Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 2592
GnomAD4 exome AF: 0.000191 AC: 216AN: 1131334Hom.: 2 Cov.: 31 AF XY: 0.000206 AC XY: 112AN XY: 542446
GnomAD4 genome ? AF: 0.0000723 AC: 11AN: 152094Hom.: 0 Cov.: 32 AF XY: 0.0000807 AC XY: 6AN XY: 74344
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 23 of the DNAAF5 protein (p.Glu23Asp). This variant is present in population databases (rs540763017, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with DNAAF5-related conditions. ClinVar contains an entry for this variant (Variation ID: 1367513). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 30, 2021 | The c.69G>T (p.E23D) alteration is located in exon 1 (coding exon 1) of the DNAAF5 gene. This alteration results from a G to T substitution at nucleotide position 69, causing the glutamic acid (E) at amino acid position 23 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at