chr19-44780915-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_012116.4(CBLC):c.364G>T(p.Ala122Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,612,224 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000055 ( 0 hom. )
Consequence
CBLC
NM_012116.4 missense
NM_012116.4 missense
Scores
9
9
Clinical Significance
Conservation
PhyloP100: 6.43
Genes affected
CBLC (HGNC:15961): (Cbl proto-oncogene C) This gene encodes a member of the Cbl family of E3 ubiquitin ligases. Cbl proteins play important roles in cell signaling through the ubiquitination and subsequent downregulation of tyrosine kinases. Expression of this gene may be restricted to epithelial cells, and alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Feb 2012]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CBLC | NM_012116.4 | c.364G>T | p.Ala122Ser | missense_variant | 2/11 | ENST00000647358.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CBLC | ENST00000647358.2 | c.364G>T | p.Ala122Ser | missense_variant | 2/11 | NM_012116.4 | P1 | ||
CBLC | ENST00000341505.4 | c.364G>T | p.Ala122Ser | missense_variant | 2/10 | 1 | |||
CBLC | ENST00000647063.1 | upstream_gene_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152232Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000802 AC: 2AN: 249462Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135036
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GnomAD4 exome AF: 0.00000548 AC: 8AN: 1459992Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6AN XY: 726294
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GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152232Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74380
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 23, 2024 | The c.364G>T (p.A122S) alteration is located in exon 2 (coding exon 2) of the CBLC gene. This alteration results from a G to T substitution at nucleotide position 364, causing the alanine (A) at amino acid position 122 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Uncertain
T
MutationAssessor
Uncertain
M;M;M
MutationTaster
Benign
D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;N;.
REVEL
Uncertain
Sift
Benign
T;T;.
Sift4G
Benign
T;D;.
Polyphen
D;D;D
Vest4
MVP
MPC
ClinPred
D
GERP RS
Varity_R
gMVP
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