chr16-57204860-G-A
Position:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_133368.3(RSPRY1):c.202G>A(p.Val68Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Consequence
RSPRY1
NM_133368.3 missense
NM_133368.3 missense
Scores
15
Clinical Significance
Conservation
PhyloP100: 0.818
Genes affected
RSPRY1 (HGNC:29420): (ring finger and SPRY domain containing 1) This gene encodes a glycoprotein that contains a RING-type zinc finger domain and an SPRY domain of unknown function. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2015]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.050331593).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RSPRY1 | NM_133368.3 | c.202G>A | p.Val68Ile | missense_variant | 2/15 | ENST00000394420.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RSPRY1 | ENST00000394420.9 | c.202G>A | p.Val68Ile | missense_variant | 2/15 | 1 | NM_133368.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
Cov.:
32
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome Cov.: 32
GnomAD4 genome
Cov.:
32
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Mar 27, 2021 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RSPRY1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with isoleucine at codon 68 of the RSPRY1 protein (p.Val68Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
N;N
PrimateAI
Benign
T
PROVEAN
Benign
N;N;N;N;N;N
Sift
Benign
T;T;T;T;T;D
Sift4G
Benign
T;T;T;T;T;T
Polyphen
0.0080
.;.;B;.;B;.
Vest4
0.031, 0.036
MutPred
Gain of glycosylation at S66 (P = 0.1682);Gain of glycosylation at S66 (P = 0.1682);Gain of glycosylation at S66 (P = 0.1682);Gain of glycosylation at S66 (P = 0.1682);Gain of glycosylation at S66 (P = 0.1682);Gain of glycosylation at S66 (P = 0.1682);
MVP
MPC
0.64
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at