rs186332019
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBP6
The NM_024700.4(SNIP1):c.559C>T(p.Arg187Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000116 in 1,614,102 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R187Q) has been classified as Likely benign.
Frequency
Consequence
NM_024700.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SNIP1 | NM_024700.4 | c.559C>T | p.Arg187Trp | missense_variant | 3/4 | ENST00000296215.8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SNIP1 | ENST00000296215.8 | c.559C>T | p.Arg187Trp | missense_variant | 3/4 | 1 | NM_024700.4 | P1 | |
SNIP1 | ENST00000638725.1 | n.1071C>T | non_coding_transcript_exon_variant | 1/2 | 2 | ||||
SNIP1 | ENST00000468040.2 | c.*333C>T | 3_prime_UTR_variant, NMD_transcript_variant | 4/5 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152094Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000382 AC: 96AN: 251470Hom.: 0 AF XY: 0.000302 AC XY: 41AN XY: 135906
GnomAD4 exome AF: 0.000116 AC: 170AN: 1461890Hom.: 0 Cov.: 31 AF XY: 0.0000894 AC XY: 65AN XY: 727246
GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152212Hom.: 1 Cov.: 32 AF XY: 0.000121 AC XY: 9AN XY: 74408
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Jul 13, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 17, 2024 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 16, 2023 | Variant summary: SNIP1 c.559C>T (p.Arg187Trp) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00038 in 251470 control chromosomes, predominantly at a frequency of 0.0026 within the Latino subpopulation in the gnomAD database. To our knowledge, no occurrence of c.559C>T in individuals affected with Psychomotor Retardation, Epilepsy, And Craniofacial Dysmorphism and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign and VUS. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at