19-5733883-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_152784.4(CATSPERD):​c.304C>T​(p.His102Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,612,484 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 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000034 ( 0 hom. )

Consequence

CATSPERD
NM_152784.4 missense

Scores

1
5
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.13
Variant links:
Genes affected
CATSPERD (HGNC:28598): (cation channel sperm associated auxiliary subunit delta) Predicted to be involved in flagellated sperm motility and sperm capacitation. Predicted to be located in sperm principal piece. Predicted to be part of CatSper complex. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.3663891).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CATSPERDNM_152784.4 linkc.304C>T p.His102Tyr missense_variant Exon 5 of 22 ENST00000381624.4 NP_689997.3 Q86XM0-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CATSPERDENST00000381624.4 linkc.304C>T p.His102Tyr missense_variant Exon 5 of 22 1 NM_152784.4 ENSP00000371037.3 Q86XM0-1

Frequencies

GnomAD3 genomes
AF:
0.0000395
AC:
6
AN:
152070
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000242
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000656
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000362
AC:
9
AN:
248474
Hom.:
0
AF XY:
0.0000371
AC XY:
5
AN XY:
134824
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.0000293
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000331
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000619
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000342
AC:
50
AN:
1460414
Hom.:
0
Cov.:
30
AF XY:
0.0000413
AC XY:
30
AN XY:
726526
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000186
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000306
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000395
AC:
6
AN:
152070
Hom.:
0
Cov.:
31
AF XY:
0.0000404
AC XY:
3
AN XY:
74284
show subpopulations
Gnomad4 AFR
AF:
0.0000242
Gnomad4 AMR
AF:
0.0000656
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000441
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000712
Hom.:
0
Bravo
AF:
0.0000302
ExAC
AF:
0.0000497
AC:
6
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000178

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 08, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.304C>T (p.H102Y) alteration is located in exon 5 (coding exon 5) of the CATSPERD gene. This alteration results from a C to T substitution at nucleotide position 304, causing the histidine (H) at amino acid position 102 to be replaced by a tyrosine (Y). 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
0.19
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.56
CADD
Benign
15
DANN
Uncertain
0.98
DEOGEN2
Benign
0.011
T
Eigen
Benign
-0.23
Eigen_PC
Benign
-0.44
FATHMM_MKL
Benign
0.070
N
LIST_S2
Benign
0.48
T
M_CAP
Benign
0.0055
T
MetaRNN
Benign
0.37
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.0
M
PrimateAI
Uncertain
0.52
T
PROVEAN
Uncertain
-2.6
D
REVEL
Benign
0.069
Sift
Uncertain
0.0060
D
Sift4G
Pathogenic
0.0
D
Polyphen
0.94
P
Vest4
0.59
MutPred
0.46
Loss of disorder (P = 0.0539);
MVP
0.25
MPC
0.72
ClinPred
0.24
T
GERP RS
0.38
Varity_R
0.20
gMVP
0.44

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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.

Other links and lift over

dbSNP: rs755637505; hg19: chr19-5733894; API