Genetic Variant CABYR:p.Val168Ile (chr18-24156003-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_153769.3(CABYR):c.502G>A(p.Val168Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,886 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000062 ( 0 hom. )

Consequence

CABYR
NM_153769.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.58

Publications

2 publications found

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 was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.24837345).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153769.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CABYR	NM_153769.3	MANE Select	c.502G>A	p.Val168Ile	missense	Exon 4 of 6	NP_722453.1	O75952-3
CABYR	NM_012189.4		c.502G>A	p.Val168Ile	missense	Exon 4 of 6	NP_036321.2
CABYR	NM_153768.3		c.448G>A	p.Val150Ile	missense	Exon 3 of 5	NP_722452.1	O75952-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CABYR	ENST00000399496.8	TSL:1 MANE Select	c.502G>A	p.Val168Ile	missense	Exon 4 of 6	ENSP00000382419.3	O75952-3
CABYR	ENST00000621648.4	TSL:1	c.502G>A	p.Val168Ile	missense	Exon 4 of 6	ENSP00000483621.1	O75952-1
CABYR	ENST00000399481.6	TSL:1	c.448G>A	p.Val150Ile	missense	Exon 3 of 5	ENSP00000382404.3	O75952-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000239

AC:

AN:

251376

AF XY:

0.0000221

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000326

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000616

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000550

AC XY:

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000756

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1112006

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000165

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.36

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.040

Eigen

Pathogenic

0.70

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.71

M_CAP

Benign

0.0089

MetaRNN

Benign

0.25

MetaSVM

Benign

-0.46

MutationAssessor

Benign

1.8

PhyloP100

2.6

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.39

REVEL

Benign

0.17

Sift

Uncertain

0.026

Sift4G

Uncertain

0.036

Polyphen

1.0

Vest4

0.19

MutPred

0.43

Loss of sheet (P = 0.0817)

MVP

0.57

MPC

0.11

ClinPred

0.47

GERP RS

6.0

PromoterAI

-0.040

Neutral

(source)

Varity_R

0.097

gMVP

0.061

Mutation Taster

=88/12

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over