19-50422868-C-G
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_003121.5(SPIB):c.170C>G(p.Pro57Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000124 in 1,610,046 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P57S) has been classified as Likely benign.
Frequency
Consequence
NM_003121.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SPIB | NM_003121.5 | c.170C>G | p.Pro57Arg | missense_variant | 4/6 | ENST00000595883.6 | |
SPIB | NM_001244000.2 | c.112C>G | p.Pro38Ala | missense_variant | 4/6 | ||
SPIB | NM_001243999.2 | c.170C>G | p.Pro57Arg | missense_variant | 4/6 | ||
SPIB | NM_001243998.2 | c.66+323C>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SPIB | ENST00000595883.6 | c.170C>G | p.Pro57Arg | missense_variant | 4/6 | 1 | NM_003121.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000132 AC: 2AN: 152022Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000122 AC: 3AN: 246890Hom.: 0 AF XY: 0.0000150 AC XY: 2AN XY: 133728
GnomAD4 exome AF: 0.0000123 AC: 18AN: 1458024Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 725158
GnomAD4 genome ? AF: 0.0000132 AC: 2AN: 152022Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74232
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 26, 2022 | The c.170C>G (p.P57R) alteration is located in exon 1 (coding exon 1) of the SPIB gene. This alteration results from a C to G substitution at nucleotide position 170, causing the proline (P) at amino acid position 57 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at