chr11-66018882-C-T

Variant names:

• chr11-66018882-C-T
• rs1309679651
• NM_053054.4:c.2146G>A

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.2146G>A​(p.Glu716Lys) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CATSPER1 NM_053054.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.04
• Publications: 1 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=0.24864805).

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.2146G>A	p.Glu716Lys	missense	Exon 10 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.2146G>A	p.Glu716Lys	missense	Exon 10 of 12	ENSP00000309052.5	Q8NEC5
	CATSPER1	ENST00000529244.1	TSL:3	n.347G>A		non_coding_transcript_exon	Exon 4 of 6
	ENSG00000295293	ENST00000729053.1		n.250+1958C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.098	D
BayesDel_noAF	Benign	-0.10
CADD	Benign	18
DANN	Uncertain	1.0
DEOGEN2	Benign	0.17	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.51
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.63	T
M_CAP	Uncertain	0.16	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Benign	2.0	M
PhyloP100		2.0
PrimateAI	Benign	0.39	T
PROVEAN	Uncertain	-2.7	D
REVEL	Uncertain	0.33
Sift	Uncertain	0.020	D
Sift4G	Uncertain	0.010	D
Polyphen		0.96	D
Vest4		0.23
MutPred		0.35		Gain of MoRF binding (P = 0.0051)
MVP		0.88
MPC		0.54
ClinPred		0.69	D
GERP RS		2.8
Varity_R		0.14
gMVP		0.28
Mutation Taster		=93/7	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: rs1309679651; hg19: chr11-65786353;