chr5-142314337-C-T
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PS1_ModerateBP4_ModerateBP6BS2
The NM_001127496.3(SPRY4):c.772G>A(p.Val258Met) variant causes a missense change. The variant allele was found at a frequency of 0.000488 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt.
Frequency
Consequence
NM_001127496.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPRY4 | NM_001127496.3 | c.772G>A | p.Val258Met | missense_variant | 2/2 | ENST00000434127.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPRY4 | ENST00000434127.3 | c.772G>A | p.Val258Met | missense_variant | 2/2 | 1 | NM_001127496.3 | P1 | |
SPRY4 | ENST00000344120.4 | c.841G>A | p.Val281Met | missense_variant | 3/3 | 1 | |||
SPRY4 | ENST00000643792.1 | n.1454G>A | non_coding_transcript_exon_variant | 1/1 |
Frequencies
GnomAD3 genomes ? AF: 0.000335 AC: 51AN: 152224Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000263 AC: 66AN: 250662Hom.: 0 AF XY: 0.000302 AC XY: 41AN XY: 135626
GnomAD4 exome AF: 0.000504 AC: 736AN: 1461706Hom.: 0 Cov.: 32 AF XY: 0.000468 AC XY: 340AN XY: 727186
GnomAD4 genome ? AF: 0.000335 AC: 51AN: 152342Hom.: 0 Cov.: 32 AF XY: 0.000295 AC XY: 22AN XY: 74478
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2022 | SPRY4: BS1 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 19, 2022 | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 281 of the SPRY4 protein (p.Val281Met). This variant is present in population databases (rs200364529, gnomAD 0.05%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of SPRY4-related conditions (PMID: 23643382). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. - |
SPRY4-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Dec 28, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at