chr10-122461728-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_002775.5(HTRA1):c.76C>T(p.Arg26Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000677 in 1,181,404 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R26Q) has been classified as Likely benign.
Frequency
Consequence
NM_002775.5 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 |
---|---|---|---|---|---|---|---|
HTRA1 | NM_002775.5 | c.76C>T | p.Arg26Trp | missense_variant | 1/9 | ENST00000368984.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
HTRA1 | ENST00000368984.8 | c.76C>T | p.Arg26Trp | missense_variant | 1/9 | 1 | NM_002775.5 | P1 | |
HTRA1 | ENST00000648167.1 | c.154+3019C>T | intron_variant |
Frequencies
GnomAD3 genomes AF: 0.0000271 AC: 4AN: 147756Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.00000387 AC: 4AN: 1033648Hom.: 0 Cov.: 30 AF XY: 0.00000199 AC XY: 1AN XY: 503252
GnomAD4 genome AF: 0.0000271 AC: 4AN: 147756Hom.: 0 Cov.: 32 AF XY: 0.0000417 AC XY: 3AN XY: 71926
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 28, 2023 | The c.76C>T (p.R26W) alteration is located in exon 1 (coding exon 1) of the HTRA1 gene. This alteration results from a C to T substitution at nucleotide position 76, causing the arginine (R) at amino acid position 26 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