18-24156247-C-T
Position:
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The ENST00000399496.8(CABYR):c.541+205C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,614,056 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 (★).
Frequency
Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000012 ( 0 hom. )
Consequence
CABYR
ENST00000399496.8 intron
ENST00000399496.8 intron
Scores
2
17
Clinical Significance
Conservation
PhyloP100: 0.140
Genes affected
CABYR (HGNC:15569): (calcium binding tyrosine phosphorylation regulated) To reach fertilization competence, spermatozoa undergo a series of morphological and molecular maturational processes, termed capacitation, involving protein tyrosine phosphorylation and increased intracellular calcium. The protein encoded by this gene localizes to the principal piece of the sperm flagellum in association with the fibrous sheath and exhibits calcium-binding when phosphorylated during capacitation. A pseudogene on chromosome 3 has been identified for this gene. Alternatively spliced transcript variants encoding distinct protein isoforms have been found for this gene. [provided by RefSeq, Jul 2013]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.01585403).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
CABYR | NM_153769.3 | c.541+205C>T | intron_variant | ENST00000399496.8 | NP_722453.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
CABYR | ENST00000399496.8 | c.541+205C>T | intron_variant | 1 | NM_153769.3 | ENSP00000382419 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152098Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000603 AC: 15AN: 248824Hom.: 0 AF XY: 0.0000594 AC XY: 8AN XY: 134708
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GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461840Hom.: 0 Cov.: 32 AF XY: 0.0000124 AC XY: 9AN XY: 727216
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GnomAD4 genome AF: 0.0000460 AC: 7AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74410
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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 | Dec 11, 2023 | The c.746C>T (p.P249L) alteration is located in exon 4 (coding exon 3) of the CABYR gene. This alteration results from a C to T substitution at nucleotide position 746, causing the proline (P) at amino acid position 249 to be replaced by a leucine (L). 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
Benign
DANN
Benign
DEOGEN2
Benign
T;.;T;T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T;T;.;.;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
.;.;L;L;L
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
.;.;N;.;.
REVEL
Benign
Sift
Uncertain
.;.;D;.;.
Sift4G
Uncertain
D;D;D;D;D
Polyphen
0.88, 0.61
.;P;P;P;P
Vest4
MutPred
0.22
.;.;Loss of methylation at K250 (P = 0.0573);Loss of methylation at K250 (P = 0.0573);Loss of methylation at K250 (P = 0.0573);
MVP
ClinPred
T
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