11-66017131-C-A

Variant names:

• chr11-66017131-C-A
• rs370395617
• NM_053054.4:c.2245G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_053054.4(CATSPER1):​c.2245G>T​(p.Val749Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 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. V749M) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: CATSPER1 NM_053054.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 0 publications found

Genes affected

CATSPER1 (HGNC:17116): (cation channel sperm associated 1) Calcium ions play a primary role in the regulation of sperm motility. This gene belongs to a family of putative cation channels that are specific to spermatozoa and localize to the flagellum. The protein family features a single repeat with six membrane-spanning segments and a predicted calcium-selective pore region. [provided by RefSeq, Jul 2008]

CATSPER1 Gene-Disease associations (from GenCC):

• non-syndromic male infertility due to sperm motility disorder

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• spermatogenic failure 7

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ENSG00000295293 (HGNC:):

ACMG classification

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=0.18876979).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_053054.4. 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
	CATSPER1	NM_053054.4	MANE Select	c.2245G>T	p.Val749Leu	missense	Exon 11 of 12	NP_444282.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER1	ENST00000312106.6	TSL:1 MANE Select	c.2245G>T	p.Val749Leu	missense	Exon 11 of 12	ENSP00000309052.5	Q8NEC5
	CATSPER1	ENST00000529244.1	TSL:3	n.485G>T		non_coding_transcript_exon	Exon 5 of 6
	ENSG00000295293	ENST00000729053.1		n.250+207C>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.52
BayesDel_addAF	Uncertain	0.064	T
BayesDel_noAF	Benign	-0.15
CADD	Benign	12
DANN	Uncertain	0.99
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.17
FATHMM_MKL	Benign	0.47	N
LIST_S2	Benign	0.56	T
M_CAP	Uncertain	0.093	D
MetaRNN	Benign	0.19	T
MetaSVM	Uncertain	0.21	D
MutationAssessor	Benign	1.4	L
PhyloP100		1.0
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.27
Sift	Benign	0.18	T
Sift4G	Pathogenic	0.0	D
Polyphen		0.79	P
Vest4		0.25
MutPred		0.29		Gain of relative solvent accessibility (P = 0.0522)
MVP		0.90
MPC		0.44
ClinPred		0.55	D
GERP RS		4.5
Varity_R		0.12
gMVP		0.24
Mutation Taster		=92/8	polymorphism

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: rs370395617; hg19: chr11-65784602;