9-137878108-T-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_000718.4(CACNA1B):āc.175T>Cā(p.Tyr59His) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Consequence
NM_000718.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CACNA1B | NM_000718.4 | c.175T>C | p.Tyr59His | missense_variant | Exon 1 of 47 | ENST00000371372.6 | NP_000709.1 | |
CACNA1B | NM_001243812.2 | c.175T>C | p.Tyr59His | missense_variant | Exon 1 of 47 | NP_001230741.1 | ||
LOC100133077 | NR_121583.1 | n.2692-2428A>G | intron_variant | Intron 2 of 3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CACNA1B | ENST00000371372.6 | c.175T>C | p.Tyr59His | missense_variant | Exon 1 of 47 | 5 | NM_000718.4 | ENSP00000360423.1 | ||
CACNA1B | ENST00000371357.5 | c.175T>C | p.Tyr59His | missense_variant | Exon 1 of 46 | 5 | ENSP00000360408.1 | |||
CACNA1B | ENST00000371363.5 | c.175T>C | p.Tyr59His | missense_variant | Exon 1 of 46 | 5 | ENSP00000360414.1 | |||
CACNA1B | ENST00000277551.6 | c.175T>C | p.Tyr59His | missense_variant | Exon 1 of 47 | 5 | ENSP00000277551.2 |
Frequencies
GnomAD3 genomes Cov.: 34
GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0AN: 1196320Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 582392
GnomAD4 genome Cov.: 34
ClinVar
Submissions by phenotype
not provided Uncertain:1
This 18 year old female with moderate intellectual disability, macrocephaly, and seizure disorder was found to carry a missense variant in CACNA1B. More evidence is needed to explore the link between variants in the CACNA1B gene and human disease. While the function of CACNA1B has not been completely defined, mice lacking CACNA1B function had altered memory, learning, sleep-wake cycles, and pain responses as well as aggressive behavior (Kim et al., 2001; Ino et al., 2001). Parental samples are unavailable for this patient, so inheritance is unknown. The variant is not present in population databases. Computational models predict the variant to be probably damaging. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at