10-22389235-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate
The NM_012443.4(SPAG6):c.928C>T(p.Arg310Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000118 in 1,613,038 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R310L) has been classified as Uncertain significance.
Frequency
Consequence
NM_012443.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPAG6 | NM_012443.4 | c.928C>T | p.Arg310Trp | missense_variant | 7/11 | ENST00000376624.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPAG6 | ENST00000376624.8 | c.928C>T | p.Arg310Trp | missense_variant | 7/11 | 1 | NM_012443.4 | P1 | |
ENST00000422675.1 | n.251-23614C>T | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes AF: 0.0000329 AC: 5AN: 152114Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 251010Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 135660
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1460924Hom.: 0 Cov.: 31 AF XY: 0.00000550 AC XY: 4AN XY: 726742
GnomAD4 genome AF: 0.0000329 AC: 5AN: 152114Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74306
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 13, 2023 | The c.928C>T (p.R310W) alteration is located in exon 7 (coding exon 7) of the SPAG6 gene. This alteration results from a C to T substitution at nucleotide position 928, causing the arginine (R) at amino acid position 310 to be replaced by a tryptophan (W). 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