11-64300838-C-T

Variant names:

• chr11-64300838-C-T
• rs2286614
• NM_001039496.2:c.203C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 39 publications found

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]

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]

ACMG classification

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	c.203C>T	p.Pro68Leu	missense_variant	Exon 2 of 5	ENST00000328404.8	NP_001034585.1
KCNK4-CATSPERZ	NR_133662.1	n.2210C>T		non_coding_transcript_exon_variant	Exon 8 of 11

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.119 AC: 18033 AN: 152122 Hom.: 1355 Cov.: 33

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

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.: 33 AF XY: 0.148 AC XY: 103094 AN XY: 694946

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

GnomAD4 genome AF: 0.118 AC: 18037 AN: 152240 Hom.: 1354 Cov.: 33 AF XY: 0.119 AC XY: 8824 AN XY: 74428

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: 46 AN: 294

European-Non Finnish (NFE) AF: 0.159 AC: 10785 AN: 68012

Other (OTH) AF: 0.151 AC: 320 AN: 2116

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	T
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.056
DANN	Benign	0.81
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.46	T;T
MetaRNN	Benign	0.0046	T;T
MetaSVM	Benign	-1.0	T
PhyloP100		-1.8
PrimateAI	Benign	0.22	T
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	T
GERP RS		-6.6
PromoterAI		-0.0031	Neutral
Varity_R		0.025
gMVP		0.021
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2286614; hg19: chr11-64068310; COSMIC: COSV107196318; COSMIC: COSV107196318;