12-57258952-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001394031.1(R3HDM2):c.2239T>C(p.Tyr747His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000322 in 1,612,660 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_001394031.1 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
R3HDM2 | NM_001394031.1 | c.2239T>C | p.Tyr747His | missense_variant | Exon 20 of 24 | ENST00000402412.6 | NP_001380960.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
R3HDM2 | ENST00000402412.6 | c.2239T>C | p.Tyr747His | missense_variant | Exon 20 of 24 | 1 | NM_001394031.1 | ENSP00000385839.1 | ||
ENSG00000258830 | ENST00000548184.1 | n.*1289T>C | non_coding_transcript_exon_variant | Exon 10 of 15 | 2 | ENSP00000477227.1 | ||||
ENSG00000258830 | ENST00000548184.1 | n.*1289T>C | 3_prime_UTR_variant | Exon 10 of 15 | 2 | ENSP00000477227.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152174Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 251094Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135702
GnomAD4 exome AF: 0.0000336 AC: 49AN: 1460486Hom.: 0 Cov.: 31 AF XY: 0.0000358 AC XY: 26AN XY: 726584
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152174Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74336
ClinVar
Submissions by phenotype
not specified Uncertain:1
The c.2197T>C (p.Y733H) alteration is located in exon 18 (coding exon 18) of the R3HDM2 gene. This alteration results from a T to C substitution at nucleotide position 2197, causing the tyrosine (Y) at amino acid position 733 to be replaced by a histidine (H). 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