chr19-5739326-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_152784.4(CATSPERD):​c.460C>T​(p.His154Tyr) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000668 in 1,423,016 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 31)
Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

CATSPERD
NM_152784.4 missense, splice_region

Scores

2
17
Splicing: ADA: 0.00008225
2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.354
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 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=0.018452257).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CATSPERDNM_152784.4 linkc.460C>T p.His154Tyr missense_variant, splice_region_variant Exon 7 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.460C>T p.His154Tyr missense_variant, splice_region_variant Exon 7 of 22 1 NM_152784.4 ENSP00000371037.3 Q86XM0-1

Frequencies

GnomAD3 genomes
AF:
0.000353
AC:
53
AN:
150332
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.00115
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000200
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00146
GnomAD3 exomes
AF:
0.0000736
AC:
17
AN:
231000
Hom.:
0
AF XY:
0.0000636
AC XY:
8
AN XY:
125768
show subpopulations
Gnomad AFR exome
AF:
0.00101
Gnomad AMR exome
AF:
0.0000638
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:
0.0000330
AC:
42
AN:
1272570
Hom.:
0
Cov.:
20
AF XY:
0.0000405
AC XY:
26
AN XY:
642044
show subpopulations
Gnomad4 AFR exome
AF:
0.00102
Gnomad4 AMR exome
AF:
0.0000989
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:
0.00000209
Gnomad4 OTH exome
AF:
0.000130
GnomAD4 genome
AF:
0.000352
AC:
53
AN:
150446
Hom.:
0
Cov.:
31
AF XY:
0.000313
AC XY:
23
AN XY:
73418
show subpopulations
Gnomad4 AFR
AF:
0.00115
Gnomad4 AMR
AF:
0.000199
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00144
Alfa
AF:
0.0000360
Hom.:
0
Bravo
AF:
0.000465
ESP6500AA
AF:
0.00166
AC:
6
ESP6500EA
AF:
0.00
AC:
0
ExAC
AF:
0.0000911
AC:
11

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 24, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.460C>T (p.H154Y) alteration is located in exon 7 (coding exon 7) of the CATSPERD gene. This alteration results from a C to T substitution at nucleotide position 460, causing the histidine (H) at amino acid position 154 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
0.11
BayesDel_addAF
Benign
-0.65
T
BayesDel_noAF
Benign
-0.76
CADD
Benign
3.6
DANN
Benign
0.77
DEOGEN2
Benign
0.0024
T
Eigen
Benign
-1.5
Eigen_PC
Benign
-1.6
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.34
T
M_CAP
Benign
0.0023
T
MetaRNN
Benign
0.018
T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
0.0
N
PrimateAI
Benign
0.37
T
PROVEAN
Benign
-1.3
N
REVEL
Benign
0.032
Sift
Uncertain
0.0040
D
Sift4G
Uncertain
0.011
D
Polyphen
0.10
B
Vest4
0.17
MVP
0.040
MPC
0.25
ClinPred
0.012
T
GERP RS
-6.0
Varity_R
0.089
gMVP
0.25

Splicing

Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
0.000082
dbscSNV1_RF
Benign
0.016
SpliceAI score (max)
0.090
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: rs200285271; hg19: chr19-5739337; API