Variant chr18-24156348-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The ENST00000621648.4(CABYR):c.847G>C(p.Ala283Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

CABYR
ENST00000621648.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.53

Variant links:

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]

CABYR links:

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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	Protein	UniProt
CABYR	NM_153769.3 linkuse as main transcript	c.541+306G>C		intron_variant		ENST00000399496.8	NP_722453.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CABYR	ENST00000399496.8 linkuse as main transcript	c.541+306G>C		intron_variant		1	NM_153769.3	ENSP00000382419	P1	O75952-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000402

AC:

AN:

249006

Hom.:

AF XY:

0.00

AC XY:

AN XY:

134786

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Feb 21, 2024

The c.847G>C (p.A283P) alteration is located in exon 4 (coding exon 3) of the CABYR gene. This alteration results from a G to C substitution at nucleotide position 847, causing the alanine (A) at amino acid position 283 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.099

BayesDel_noAF

Uncertain

-0.010

CADD

Benign

DANN

Benign

0.92

DEOGEN2

Benign

0.081

T;.;T;T;T

Eigen

Uncertain

0.38

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.73

T;T;.;.;T

M_CAP

Benign

0.0072

MetaRNN

Uncertain

0.44

T;T;T;T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

1.8

.;.;L;L;L

MutationTaster

Benign

0.81

PrimateAI

Benign

0.42

PROVEAN

Benign

-0.75

.;.;N;.;.

REVEL

Benign

0.14

Sift

Pathogenic

0.0

.;.;D;.;.

Sift4G

Benign

0.31

T;T;T;T;T

Polyphen

1.0, 1.0

.;D;D;D;D

Vest4

0.64

MutPred

0.35

.;.;Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);Loss of sheet (P = 0.0054);

MVP

0.39

ClinPred

0.83

GERP RS

4.6

Varity_R

0.41

gMVP

0.53

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

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