Genetic Variant NM_001039496.2:c.203C>T (chr11-64300838-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001039496.2(CATSPERZ):c.203C>T(p.Pro68Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 1,559,112 control chromosomes in the GnomAD database, including 17,728 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.12 ( 1354 hom., cov: 33)

Exomes 𝑓: 0.15 ( 16374 hom. )

Consequence

CATSPERZ
NM_001039496.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.84

Publications

39 publications found

Variant links:

Genes affected

CATSPERZ (HGNC:19231): (catsper channel auxiliary subunit zeta) Predicted to be involved in flagellated sperm motility; male meiotic nuclear division; and sperm capacitation. Located in cytoplasm and sperm principal piece. [provided by Alliance of Genome Resources, Apr 2022]

CATSPERZ links:

KCNK4-CATSPERZ (HGNC:56753): (KCNK4-CATSPERZ readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring KCNK4 (potassium channel subfamily K member 4) and the downstream TEX40 (testis expressed 40) chromosome 11. The readthrough transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Nov 2015]

KCNK4-CATSPERZ links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0045560896).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.156 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CATSPERZ	NM_001039496.2 link	c.203C>T	p.Pro68Leu	missense_variant	Exon 2 of 5	ENST00000328404.8	NP_001034585.1	Q9NTU4
KCNK4-CATSPERZ	NR_133662.1 link	n.2210C>T		non_coding_transcript_exon_variant	Exon 8 of 11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CATSPERZ	ENST00000328404.8 link	c.203C>T	p.Pro68Leu	missense_variant	Exon 2 of 5	1	NM_001039496.2	ENSP00000491717.1	Q9NTU4
KCNK4-CATSPERZ	ENST00000539086.5 link	n.2210C>T		non_coding_transcript_exon_variant	Exon 8 of 11	1
CATSPERZ	ENST00000539943.1 link	c.77C>T	p.Pro26Leu	missense_variant	Exon 1 of 4	2		ENSP00000443917.1	F5H186

Frequencies

GnomAD3 genomes

AF:

0.119

AC:

18033

AN:

152122

Hom.:

1355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0427

Gnomad AMI

AF:

0.107

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.107

Gnomad EAS

AF:

0.113

Gnomad SAS

AF:

0.0710

Gnomad FIN

AF:

0.166

Gnomad MID

AF:

0.152

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.146

GnomAD2 exomes

AF:

0.130

AC:

21111

AN:

162324

AF XY:

0.131

show subpopulations

Gnomad AFR exome

AF:

0.0393

Gnomad AMR exome

AF:

0.108

Gnomad ASJ exome

AF:

0.112

Gnomad EAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.160

Gnomad NFE exome

AF:

0.163

Gnomad OTH exome

AF:

0.147

GnomAD4 exome

AF:

0.149

AC:

209996

AN:

1406872

Hom.:

16374

Cov.:

AF XY:

0.148

AC XY:

103094

AN XY:

694946

show subpopulations

African (AFR)

AF:

0.0371

AC:

1186

AN:

31988

American (AMR)

AF:

0.108

AC:

3923

AN:

36344

Ashkenazi Jewish (ASJ)

AF:

0.113

AC:

2862

AN:

25276

East Asian (EAS)

AF:

0.106

AC:

3828

AN:

36272

South Asian (SAS)

AF:

0.0826

AC:

6591

AN:

79798

European-Finnish (FIN)

AF:

0.160

AC:

7755

AN:

48452

Middle Eastern (MID)

AF:

0.169

AC:

964

AN:

5708

European-Non Finnish (NFE)

AF:

0.160

AC:

174081

AN:

1084646

Other (OTH)

AF:

0.151

AC:

8806

AN:

58388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

11401

22802

34203

45604

57005

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6150

12300

18450

24600

30750

<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

AF:

0.118

AC:

18037

AN:

152240

Hom.:

1354

Cov.:

AF XY:

0.119

AC XY:

8824

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.0426

AC:

1768

AN:

41550

American (AMR)

AF:

0.128

AC:

1962

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.107

AC:

370

AN:

3472

East Asian (EAS)

AF:

0.112

AC:

580

AN:

5156

South Asian (SAS)

AF:

0.0714

AC:

345

AN:

4830

European-Finnish (FIN)

AF:

0.166

AC:

1764

AN:

10600

Middle Eastern (MID)

AF:

0.156

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10785

AN:

68012

Other (OTH)

AF:

0.151

AC:

320

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

824

1648

2472

3296

4120

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

200

400

600

800

1000

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.144

Hom.:

4931

Bravo

AF:

0.113

TwinsUK

AF:

0.157

AC:

582

ALSPAC

AF:

0.157

AC:

606

ESP6500AA

AF:

0.0430

AC:

167

ESP6500EA

AF:

0.143

AC:

1167

ExAC

AF:

0.0883

AC:

9737

Asia WGS

AF:

0.115

AC:

398

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.82

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.056

(source)

DANN

Benign

0.81

DEOGEN2

Benign

0.011

T;.

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.011

LIST_S2

Benign

0.46

T;T

MetaRNN

Benign

0.0046

T;T

MetaSVM

Benign

-1.0

PhyloP100

-1.8

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.2

.;N

REVEL

Benign

0.014

Sift

Benign

0.28

.;T

Sift4G

Benign

0.091

.;T

Polyphen

0.0020

B;.

Vest4

0.014

MPC

0.50

ClinPred

0.0034

GERP RS

-6.6

PromoterAI

-0.0031

Neutral

(source)

Varity_R

0.025

gMVP

0.021

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over