1-110060806-T-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 2P and 3B. PM2BP4_ModerateBS1_Supporting
The NM_006492.3(ALX3):c.959A>G(p.Tyr320Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000075 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_006492.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ALX3 | NM_006492.3 | c.959A>G | p.Tyr320Cys | missense_variant | 4/4 | ENST00000647563.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ALX3 | ENST00000647563.2 | c.959A>G | p.Tyr320Cys | missense_variant | 4/4 | NM_006492.3 | P1 | ||
ENST00000554749.1 | n.2467T>C | non_coding_transcript_exon_variant | 1/1 | ||||||
ALX3 | ENST00000649954.1 | c.530A>G | p.Tyr177Cys | missense_variant | 3/3 | ||||
STRIP1 | ENST00000473429.5 | n.4213+6004T>C | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000438 AC: 11AN: 250942Hom.: 0 AF XY: 0.0000442 AC XY: 6AN XY: 135710
GnomAD4 exome AF: 0.0000780 AC: 114AN: 1461672Hom.: 0 Cov.: 34 AF XY: 0.0000743 AC XY: 54AN XY: 727140
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74440
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 07, 2022 | The c.959A>G (p.Y320C) alteration is located in exon 4 (coding exon 4) of the ALX3 gene. This alteration results from a A to G substitution at nucleotide position 959, causing the tyrosine (Y) at amino acid position 320 to be replaced by a cysteine (C). 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 | Jan 24, 2024 | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 320 of the ALX3 protein (p.Tyr320Cys). This variant is present in population databases (rs376262878, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ALX3-related conditions. ClinVar contains an entry for this variant (Variation ID: 2056739). 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 cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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