chr6-43645224-T-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_152732.5(RSPH9):āc.126T>Gā(p.Asp42Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,613,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D42H) has been classified as Uncertain significance.
Frequency
Consequence
NM_152732.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RSPH9 | NM_152732.5 | c.126T>G | p.Asp42Glu | missense_variant | 1/5 | ENST00000372163.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPH9 | ENST00000372163.5 | c.126T>G | p.Asp42Glu | missense_variant | 1/5 | 1 | NM_152732.5 | P1 | |
RSPH9 | ENST00000372165.8 | c.126T>G | p.Asp42Glu | missense_variant | 1/6 | 2 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152228Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000120 AC: 3AN: 250656Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135866
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461730Hom.: 0 Cov.: 32 AF XY: 0.0000110 AC XY: 8AN XY: 727180
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152228Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74376
ClinVar
Submissions by phenotype
Primary ciliary dyskinesia Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 07, 2023 | The c.126T>G (p.D42E) alteration is located in exon 1 (coding exon 1) of the RSPH9 gene. This alteration results from a T to G substitution at nucleotide position 126, causing the aspartic acid (D) at amino acid position 42 to be replaced by a glutamic acid (E). 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