Variant 11-64303837-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001039496.2(CATSPERZ):c.497G>A(p.Arg166Gln) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000684 in 1,594,308 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.00014 ( 1 hom., cov: 31)

Exomes 𝑓: 0.000061 ( 3 hom. )

Consequence

CATSPERZ
NM_001039496.2 missense, splice_region

Scores

Splicing: ADA: 0.00002654

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.40

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-TEX40 (HGNC:):

KCNK4-TEX40 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01614359).

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPERZ	NM_001039496.2 linkuse as main transcript	c.497G>A	p.Arg166Gln	missense_variant, splice_region_variant	4/5	ENST00000328404.8	NP_001034585.1	Q9NTU4
KCNK4-CATSPERZ	NR_133662.1 linkuse as main transcript	n.2504G>A		splice_region_variant, non_coding_transcript_exon_variant	10/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CATSPERZ	ENST00000328404.8 linkuse as main transcript	c.497G>A	p.Arg166Gln	missense_variant, splice_region_variant	4/5	1	NM_001039496.2	ENSP00000491717.1	Q9NTU4
KCNK4-TEX40	ENST00000539086.5 linkuse as main transcript	n.2504G>A		splice_region_variant, non_coding_transcript_exon_variant	10/11	1
CATSPERZ	ENST00000539943.1 linkuse as main transcript	c.371G>A	p.Arg124Gln	missense_variant, splice_region_variant	3/4	2		ENSP00000443917.1	F5H186
CATSPERZ	ENST00000535981.1 linkuse as main transcript	n.183G>A		splice_region_variant, non_coding_transcript_exon_variant	1/2	2

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000314

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000186

AC:

AN:

215102

Hom.:

AF XY:

0.0000258

AC XY:

AN XY:

116058

show subpopulations

Gnomad AFR exome

AF:

0.000245

Gnomad AMR exome

AF:

0.0000325

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:

0.0000610

AC:

AN:

1442100

Hom.:

Cov.:

AF XY:

0.0000615

AC XY:

AN XY:

715284

show subpopulations

Gnomad4 AFR exome

AF:

0.000972

Gnomad4 AMR exome

AF:

0.0000479

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000121

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.000586

GnomAD4 genome

AF:

0.000138

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74414

show subpopulations

Gnomad4 AFR

AF:

0.000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000987

Hom.:

Bravo

AF:

0.0000718

ESP6500AA

AF:

0.000771

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000249

AC:

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jan 31, 2022

The c.497G>A (p.R166Q) alteration is located in exon 4 (coding exon 4) of the TEX40 gene. This alteration results from a G to A substitution at nucleotide position 497, causing the arginine (R) at amino acid position 166 to be replaced by a glutamine (Q). 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

0.089

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

0.44

DANN

Benign

0.57

DEOGEN2

Benign

0.016

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0069

LIST_S2

Benign

0.49

T;T

M_CAP

Benign

0.013

MetaRNN

Benign

0.016

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.18

PROVEAN

Benign

-0.56

.;N

REVEL

Benign

0.013

Sift

Benign

0.59

.;T

Sift4G

Benign

0.32

.;T

Polyphen

0.049

B;.

Vest4

0.17

MVP

0.030

MPC

0.58

ClinPred

0.0056

GERP RS

-5.6

Varity_R

0.024

gMVP

0.011

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000027

dbscSNV1_RF

Benign

0.0

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

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