Genetic Variant NM_021185.5:c.359C>T (chr19-38343614-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_021185.5(CATSPERG):c.359C>T(p.Thr120Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000029 in 1,551,088 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

CATSPERG
NM_021185.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.301

Publications

1 publications found

Variant links:

Genes affected

CATSPERG (HGNC:25243): (cation channel sperm associated auxiliary subunit gamma) CATSPERG is a subunit of the CATSPER (see CATSPER1; MIM 606389) sperm calcium channel, which is required for sperm hyperactivated motility and male fertility (Wang et al., 2009 [PubMed 19516020]).[supplied by OMIM, Jul 2010]

CATSPERG links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.028411448).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021185.5. 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
	CATSPERG	NM_021185.5	MANE Select	c.359C>T	p.Thr120Met	missense	Exon 4 of 29	NP_067008.3
	CATSPERG	NM_001330496.2		c.359C>T	p.Thr120Met	missense	Exon 4 of 28	NP_001317425.1	B8ZZI7

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CATSPERG	ENST00000409235.8	TSL:5 MANE Select	c.359C>T	p.Thr120Met	missense	Exon 4 of 29	ENSP00000386962.3	Q6ZRH7
CATSPERG	ENST00000409410.6	TSL:1	c.359C>T	p.Thr120Met	missense	Exon 4 of 17	ENSP00000386950.2	X1WI24
CATSPERG	ENST00000410018.5	TSL:2	c.359C>T	p.Thr120Met	missense	Exon 4 of 28	ENSP00000387057.1	B8ZZI7

Frequencies

GnomAD3 genomes

AF:

0.0000788

AC:

AN:

152230

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000326

AC:

AN:

153330

AF XY:

0.0000491

show subpopulations

Gnomad AFR exome

AF:

0.000253

Gnomad AMR exome

AF:

0.0000813

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000231

GnomAD4 exome

AF:

0.0000236

AC:

AN:

1398858

Hom.:

Cov.:

AF XY:

0.0000232

AC XY:

AN XY:

689980

show subpopulations

African (AFR)

AF:

0.0000950

AC:

AN:

31588

American (AMR)

AF:

0.0000842

AC:

AN:

35636

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25146

East Asian (EAS)

AF:

0.00

AC:

AN:

35738

South Asian (SAS)

AF:

0.0000126

AC:

AN:

79216

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49120

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5658

European-Non Finnish (NFE)

AF:

0.0000222

AC:

AN:

1078766

Other (OTH)

AF:

0.0000345

AC:

AN:

57990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

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

AF:

0.0000788

AC:

AN:

152230

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74376

show subpopulations

African (AFR)

AF:

0.000217

AC:

AN:

41466

American (AMR)

AF:

0.0000654

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.000207

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10624

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.000130

Hom.:

Bravo

AF:

0.000106

ExAC

AF:

0.0000786

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.57

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.028

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.25

FATHMM_MKL

Benign

0.19

LIST_S2

Benign

0.75

M_CAP

Benign

0.0076

MetaRNN

Benign

0.028

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.4

PhyloP100

0.30

PrimateAI

Benign

0.27

PROVEAN

Benign

-0.89

REVEL

Benign

0.026

Sift

Benign

0.40

Sift4G

Benign

0.17

Polyphen

0.22

Vest4

0.17

MutPred

0.30

Gain of helix (P = 0.0425)

MVP

0.21

MPC

0.77

ClinPred

0.026

GERP RS

1.2

Varity_R

0.019

gMVP

0.42

Mutation Taster

=93/7

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over