rs779515686
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001206999.2(CIT):c.4130C>T(p.Pro1377Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,613,466 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 Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P1377P) has been classified as Likely benign.
Frequency
Consequence
NM_001206999.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CIT | NM_001206999.2 | c.4130C>T | p.Pro1377Leu | missense_variant | 32/48 | ENST00000392521.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CIT | ENST00000392521.7 | c.4130C>T | p.Pro1377Leu | missense_variant | 32/48 | 1 | NM_001206999.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 30
GnomAD3 exomes AF: 0.0000439 AC: 11AN: 250456Hom.: 0 AF XY: 0.0000369 AC XY: 5AN XY: 135474
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461304Hom.: 0 Cov.: 30 AF XY: 0.0000193 AC XY: 14AN XY: 726916
GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152162Hom.: 0 Cov.: 30 AF XY: 0.0000135 AC XY: 1AN XY: 74334
ClinVar
Submissions by phenotype
Microcephaly 17, primary, autosomal recessive Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing;provider interpretation | Geisinger Autism and Developmental Medicine Institute, Geisinger Health System | Mar 09, 2018 | This variant was identified in a 9 year old female with intellectual disability, multiple congenital anomalies, and dysmorphic facial features. The variant is present in the ExAC non-Finnish European population at 0.0027% and in the Ashkenazi Jewish population at 0.071%. In this patient, it was found to be de novo (with maternity and paternity confirmed). Computational models predict the variant to be damaging. This variant has not been reported previously in the literature, to our knowledge, and previously reported variants have not occured in this protein domain (Li, 2016; Harding, 2016; Shaheen, 2016; Basit, 2016). At the time of most recent laboratory analysis, no additional variants in the CIT gene had been identified. Whole exome sequencing also identified an additional variant of uncertain significance in another gene. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2022 | 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. 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 560261). This variant has not been reported in the literature in individuals affected with CIT-related conditions. This variant is present in population databases (rs779515686, gnomAD 0.07%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1377 of the CIT protein (p.Pro1377Leu). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at