chrX-112454804-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001395362.2(RTL4):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 0.000192 in 1,207,227 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 65 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 11/19 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_001395362.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RTL4 | NM_001395362.2 | c.76C>T | p.Arg26Trp | missense_variant | 5/5 | ENST00000695839.1 | |
RTL4 | NM_001004308.3 | c.76C>T | p.Arg26Trp | missense_variant | 3/3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RTL4 | ENST00000695839.1 | c.76C>T | p.Arg26Trp | missense_variant | 5/5 | NM_001395362.2 | P1 | ||
RTL4 | ENST00000340433.4 | c.76C>T | p.Arg26Trp | missense_variant | 4/4 | P1 | |||
RTL4 | ENST00000695808.1 | c.76C>T | p.Arg26Trp | missense_variant | 3/3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000171 AC: 19AN: 111269Hom.: 0 Cov.: 23 AF XY: 0.0000598 AC XY: 2AN XY: 33455
GnomAD3 exomes AF: 0.0000671 AC: 12AN: 178858Hom.: 0 AF XY: 0.0000783 AC XY: 5AN XY: 63840
GnomAD4 exome AF: 0.000194 AC: 213AN: 1095908Hom.: 0 Cov.: 29 AF XY: 0.000174 AC XY: 63AN XY: 361586
GnomAD4 genome ? AF: 0.000171 AC: 19AN: 111319Hom.: 0 Cov.: 23 AF XY: 0.0000597 AC XY: 2AN XY: 33517
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 15, 2023 | The c.76C>T (p.R26W) alteration is located in exon 3 (coding exon 1) of the ZCCHC16 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