chr4-56467657-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.
The NM_006947.4(SRP72):c.22G>C(p.Gly8Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000167 in 1,558,512 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G8E) has been classified as Likely benign.
Frequency
Consequence
NM_006947.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SRP72 | NM_006947.4 | c.22G>C | p.Gly8Arg | missense_variant | 1/19 | ENST00000642900.1 | |
SRP72 | NM_001267722.2 | c.22G>C | p.Gly8Arg | missense_variant | 1/17 | ||
SRP72 | XM_024454192.2 | c.22G>C | p.Gly8Arg | missense_variant | 1/17 | ||
SRP72 | NR_151856.2 | n.41G>C | non_coding_transcript_exon_variant | 1/20 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SRP72 | ENST00000642900.1 | c.22G>C | p.Gly8Arg | missense_variant | 1/19 | NM_006947.4 | P1 | ||
SRP72 | ENST00000510663.6 | c.22G>C | p.Gly8Arg | missense_variant | 1/17 | 1 | |||
SRP72 | ENST00000504757.2 | c.22G>C | p.Gly8Arg | missense_variant | 1/5 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152158Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000100 AC: 2AN: 199482Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 110676
GnomAD4 exome AF: 0.0000164 AC: 23AN: 1406354Hom.: 0 Cov.: 32 AF XY: 0.0000186 AC XY: 13AN XY: 698508
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152158Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74318
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 15, 2023 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1314214). This variant has not been reported in the literature in individuals affected with SRP72-related conditions. This variant is present in population databases (rs773611833, gnomAD 0.01%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 8 of the SRP72 protein (p.Gly8Arg). - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 29, 2021 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at