11-19192402-G-A
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PM5PP3_Moderate
The NM_003476.5(CSRP3):c.47C>T(p.Thr16Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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. T16S) has been classified as Likely pathogenic.
Frequency
Consequence
NM_003476.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CSRP3 | NM_003476.5 | c.47C>T | p.Thr16Ile | missense_variant | 2/6 | ENST00000265968.9 | |
CSRP3 | NM_001369404.1 | c.47C>T | p.Thr16Ile | missense_variant | 2/5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CSRP3 | ENST00000265968.9 | c.47C>T | p.Thr16Ile | missense_variant | 2/6 | 1 | NM_003476.5 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 26, 2010 | Variant classified as Uncertain Significance - Favor Pathogenic. Variants in the CSRP3 gene have been identified in patients with HCM as well as DCM. However, t he Thr16Ile variant has not been reported in the literature. Threonine (Thr) at position 16 is conserved across several species (including mammals, amphibians, and birds); however, fly and worm, carry a different amino acid (serine) at this position, slightly reducing the likelihood that the change detected in this ind ividual may be pathogenic. On the other hand, the variant is present in two affe cted individuals in this family, which is consistent (but does not prove) a path ogenic role. In summary, in the absence of additional data (such as family stud ies, healthy control data or functional studies) the significance of this varian t cannot be determined. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at