chr15-38253185-GAT-G
Variant summary
Our verdict is Pathogenic. Variant got 14 ACMG points: 14P and 0B. PVS1PS1_ModeratePM2PP5_Moderate
The NM_152594.3(SPRED1):c.1_2del(p.Met1?) variant causes a frameshift, start lost change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Likely pathogenic (★).
Frequency
Genomes: not found (cov: 31)
Consequence
SPRED1
NM_152594.3 frameshift, start_lost
NM_152594.3 frameshift, start_lost
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 6.46
Genes affected
SPRED1 (HGNC:20249): (sprouty related EVH1 domain containing 1) The protein encoded by this gene is a member of the Sprouty family of proteins and is phosphorylated by tyrosine kinase in response to several growth factors. The encoded protein can act as a homodimer or as a heterodimer with SPRED2 to regulate activation of the MAP kinase cascade. Defects in this gene are a cause of neurofibromatosis type 1-like syndrome (NFLS). [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Pathogenic. Variant got 14 ACMG points.
PVS1
?
Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant located near the start codon (<100nt), not predicted to undergo nonsense mediated mRNA decay. There are 107 pathogenic variants in the truncated region.
PS1
?
Another start lost variant in NM_152594.3 (SPRED1) was described as [Likely_pathogenic] in ClinVar as 930640
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 15-38253185-GAT-G is Pathogenic according to our data. Variant chr15-38253185-GAT-G is described in ClinVar as [Likely_pathogenic]. Clinvar id is 547788.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPRED1 | NM_152594.3 | c.1_2del | p.Met1? | frameshift_variant, start_lost | 1/7 | ENST00000299084.9 | |
SPRED1 | XM_005254202.4 | c.1_2del | p.Met1? | frameshift_variant, start_lost | 1/8 | ||
SPRED1 | XM_047432199.1 | c.-163_-162del | 5_prime_UTR_variant | 1/9 | |||
SPRED1 | XM_047432200.1 | c.-127_-126del | 5_prime_UTR_variant | 1/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPRED1 | ENST00000299084.9 | c.1_2del | p.Met1? | frameshift_variant, start_lost | 1/7 | 1 | NM_152594.3 | P1 | |
SPRED1 | ENST00000561317.1 | c.-127_-126del | 5_prime_UTR_variant | 1/6 | 4 | ||||
SPRED1 | ENST00000561205.1 | n.339_340del | non_coding_transcript_exon_variant | 1/5 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD3 genomes
?
Cov.:
31
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome ? Cov.: 31
GnomAD4 genome
?
Cov.:
31
ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Legius syndrome Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Center for Human Genetics, Inc, Center for Human Genetics, Inc | Nov 01, 2016 | - - |
Computational scores
Source:
Name
Calibrated prediction
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Prediction
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at