Genetic Variant CATSPERD:p.His154Tyr (chr19-5739326-C-T) – ACMG Classification: Likely_benign (-2 pts)

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

Splicing: ADA: 0.00008225

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]

CATSPERD links:

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
CATSPERD	NM_152784.4 link	c.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
CATSPERD	ENST00000381624.4 link	c.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:

AN:

150332

Hom.:

Cov.:

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:

AN:

231000

Hom.:

AF XY:

0.0000636

AC XY:

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:

AN:

1272570

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

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:

AN:

150446

Hom.:

Cov.:

AF XY:

0.000313

AC XY:

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.:

Bravo

AF:

0.000465

ESP6500AA

AF:

0.00166

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000911

AC:

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

BayesDel_noAF

Benign

-0.76

CADD

Benign

3.6

DANN

Benign

0.77

DEOGEN2

Benign

0.0024

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.34

M_CAP

Benign

0.0023

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PrimateAI

Benign

0.37

PROVEAN

Benign

-1.3

REVEL

Benign

0.032

Sift

Uncertain

0.0040

Sift4G

Uncertain

0.011

Polyphen

0.10

Vest4

0.17

MVP

0.040

MPC

0.25

ClinPred

0.012

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over