11-498808-A-G
Variant summary
Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2PP3_Strong
The NM_203387.3(RNH1):c.740T>C(p.Leu247Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000255 in 1,607,894 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 (★).
Frequency
Consequence
NM_203387.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RNH1 | NM_203387.3 | c.740T>C | p.Leu247Pro | missense_variant | Exon 7 of 11 | ENST00000354420.7 | NP_976321.1 |
Ensembl
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152232Hom.: 0 Cov.: 34
GnomAD3 exomes AF: 0.00000829 AC: 2AN: 241244Hom.: 0 AF XY: 0.00000757 AC XY: 1AN XY: 132128
GnomAD4 exome AF: 0.0000247 AC: 36AN: 1455662Hom.: 0 Cov.: 35 AF XY: 0.0000318 AC XY: 23AN XY: 724376
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152232Hom.: 0 Cov.: 34 AF XY: 0.0000269 AC XY: 2AN XY: 74372
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.740T>C (p.L247P) alteration is located in exon 7 (coding exon 5) of the RNH1 gene. This alteration results from a T to C substitution at nucleotide position 740, causing the leucine (L) at amino acid position 247 to be replaced by a proline (P). 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