Variant 11-64300939-A-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001039496.2(CATSPERZ):c.304A>G(p.Met102Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000014 in 1,428,522 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

CATSPERZ
NM_001039496.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.600

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: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-TEX40 links:

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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=0.0499897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CATSPERZ	NM_001039496.2 link	c.304A>G	p.Met102Val	missense_variant	2/5	ENST00000328404.8	NP_001034585.1	Q9NTU4
KCNK4-CATSPERZ	NR_133662.1 link	n.2311A>G		non_coding_transcript_exon_variant	8/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
CATSPERZ	ENST00000328404.8 link	c.304A>G	p.Met102Val	missense_variant	2/5	1	NM_001039496.2	ENSP00000491717.1	Q9NTU4
KCNK4-TEX40	ENST00000539086.5 link	n.2311A>G		non_coding_transcript_exon_variant	8/11	1
CATSPERZ	ENST00000539943.1 link	c.178A>G	p.Met60Val	missense_variant	1/4	2		ENSP00000443917.1	F5H186

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000526

AC:

AN:

190092

Hom.:

AF XY:

0.00

AC XY:

AN XY:

103176

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000706

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:

0.00000140

AC:

AN:

1428522

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

707366

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000264

Gnomad4 SAS exome

AF:

0.0000123

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 04, 2024

The c.304A>G (p.M102V) alteration is located in exon 2 (coding exon 2) of the TEX40 gene. This alteration results from a A to G substitution at nucleotide position 304, causing the methionine (M) at amino acid position 102 to be replaced by a valine (V). 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

0.076

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

1.6

DANN

Benign

0.67

DEOGEN2

Benign

0.0096

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.036

LIST_S2

Benign

0.33

T;T

M_CAP

Benign

0.0048

MetaRNN

Benign

0.050

T;T

MetaSVM

Benign

-1.0

PrimateAI

Benign

0.22

PROVEAN

Benign

-1.2

.;N

REVEL

Benign

0.011

Sift

Benign

0.054

.;T

Sift4G

Benign

0.28

.;T

Polyphen

0.0010

B;.

Vest4

0.016

MutPred

0.17

Gain of sheet (P = 0.0344);.;

MVP

0.030

MPC

0.50

ClinPred

0.035

GERP RS

-5.3

Varity_R

0.10

gMVP

0.040

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

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