Genetic Variant CATSPER4:p.Thr68Lys (chr1-26190830-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198137.2(CATSPER4):c.203C>A(p.Thr68Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,456,912 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T68M) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 31)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

CATSPER4
NM_198137.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.73

Publications

0 publications found

Variant links:

Genes affected

CATSPER4 (HGNC:23220): (cation channel sperm associated 4) Predicted to enable voltage-gated calcium channel activity. Predicted to be involved in flagellated sperm motility; sodium ion transport; and sperm capacitation. Predicted to be located in plasma membrane. Predicted to be part of CatSper complex. Predicted to be active in acrosomal vesicle and sperm principal piece. [provided by Alliance of Genome Resources, Apr 2022]

CATSPER4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.100263864).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198137.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER4	NM_198137.2	MANE Select	c.203C>A	p.Thr68Lys	missense	Exon 1 of 10	NP_937770.1	Q7RTX7-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CATSPER4	ENST00000456354.7	TSL:1 MANE Select	c.203C>A	p.Thr68Lys	missense	Exon 1 of 10	ENSP00000390423.3	Q7RTX7-1
CATSPER4	ENST00000518899.5	TSL:1	n.203C>A		non_coding_transcript_exon	Exon 1 of 10	ENSP00000429464.1	Q7RTX7-2
CATSPER4	ENST00000338855.6	TSL:5	c.203C>A	p.Thr68Lys	missense	Exon 1 of 9	ENSP00000341006.2	J3KNU1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1456912

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

724234

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

43972

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25994

East Asian (EAS)

AF:

0.00

AC:

AN:

39620

South Asian (SAS)

AF:

0.00

AC:

AN:

85350

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52944

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5558

European-Non Finnish (NFE)

AF:

9.01e-7

AC:

AN:

1109816

Other (OTH)

AF:

0.00

AC:

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.14

BayesDel_addAF

Uncertain

0.025

BayesDel_noAF

Benign

-0.20

CADD

Benign

0.13

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.038

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.29

M_CAP

Benign

0.068

MetaRNN

Benign

0.10

MetaSVM

Uncertain

-0.095

MutationAssessor

Benign

1.0

PhyloP100

-2.7

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

REVEL

Uncertain

0.32

Sift

Benign

0.092

Sift4G

Uncertain

0.052

Polyphen

0.35

Vest4

0.24

MutPred

0.53

Gain of ubiquitination at T68 (P = 0.0114)

MVP

0.38

MPC

0.28

ClinPred

0.091

GERP RS

-2.4

PromoterAI

-0.020

Neutral

(source)

Varity_R

0.040

gMVP

0.46

Mutation Taster

=100/0

polymorphism

(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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over