15-55430761-G-A
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_130810.4(DNAAF4):c.1172C>T(p.Ala391Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000329 in 1,460,520 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. A391A) has been classified as Likely benign.
Frequency
Consequence
NM_130810.4 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 |
---|---|---|---|---|---|---|---|
DNAAF4 | NM_130810.4 | c.1172C>T | p.Ala391Val | missense_variant | 10/10 | ENST00000321149.7 | |
DNAAF4-CCPG1 | NR_037923.1 | n.1408+1736C>T | intron_variant, non_coding_transcript_variant | ||||
DNAAF4 | NM_001033559.3 | c.1066C>T | p.Arg356Trp | missense_variant | 9/9 | ||
DNAAF4 | NM_001033560.2 | c.1047+4144C>T | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DNAAF4 | ENST00000321149.7 | c.1172C>T | p.Ala391Val | missense_variant | 10/10 | 1 | NM_130810.4 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251144Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135770
GnomAD4 exome AF: 0.0000329 AC: 48AN: 1460520Hom.: 0 Cov.: 31 AF XY: 0.0000275 AC XY: 20AN XY: 726612
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 03, 2022 | The c.1172C>T (p.A391V) alteration is located in exon 10 (coding exon 9) of the DYX1C1 gene. This alteration results from a C to T substitution at nucleotide position 1172, causing the alanine (A) at amino acid position 391 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 07, 2023 | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 391 of the DNAAF4 protein (p.Ala391Val). This variant is present in population databases (rs753571003, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with DNAAF4-related conditions. ClinVar contains an entry for this variant (Variation ID: 2167706). 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 DNAAF4 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