1-180787853-A-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_004736.4(XPR1):āc.222A>Gā(p.Ser74Ser) variant causes a splice region, synonymous change. The variant allele was found at a frequency of 0.0000418 in 1,604,740 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_004736.4 splice_region, synonymous
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
XPR1 | NM_004736.4 | c.222A>G | p.Ser74Ser | splice_region_variant, synonymous_variant | 3/15 | ENST00000367590.9 | NP_004727.2 | |
XPR1 | NM_001135669.2 | c.222A>G | p.Ser74Ser | splice_region_variant, synonymous_variant | 3/14 | NP_001129141.1 | ||
XPR1 | NM_001328662.2 | c.222A>G | p.Ser74Ser | splice_region_variant, synonymous_variant | 3/11 | NP_001315591.1 | ||
XPR1 | NR_137330.2 | n.402A>G | splice_region_variant, non_coding_transcript_exon_variant | 3/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
XPR1 | ENST00000367590.9 | c.222A>G | p.Ser74Ser | splice_region_variant, synonymous_variant | 3/15 | 1 | NM_004736.4 | ENSP00000356562.4 | ||
XPR1 | ENST00000367589.3 | c.222A>G | p.Ser74Ser | splice_region_variant, synonymous_variant | 3/14 | 1 | ENSP00000356561.3 |
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 152082Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000538 AC: 13AN: 241592Hom.: 0 AF XY: 0.0000767 AC XY: 10AN XY: 130438
GnomAD4 exome AF: 0.0000392 AC: 57AN: 1452658Hom.: 0 Cov.: 29 AF XY: 0.0000429 AC XY: 31AN XY: 722530
GnomAD4 genome AF: 0.0000658 AC: 10AN: 152082Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74294
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | May 23, 2023 | This sequence change affects codon 74 of the XPR1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the XPR1 protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs370177151, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with XPR1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2192571). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at