11-66017182-T-C

Variant names:

• chr11-66017182-T-C
• rs1326391621
• NM_053054.4:c.2202-8A>G

Variant summary

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

The NM_053054.4(CATSPER1):​c.2202-8A>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.0000061 (0 hom.)
• Consequence: CATSPER1 NM_053054.4 splice_region, intron
• Scores: Splicing: ADA: 0.000007049
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.09
• 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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.2202-8A>G		splice_region intron	N/A	NP_444282.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPER1	ENST00000312106.6	TSL:1 MANE Select	c.2202-8A>G		splice_region intron	N/A	ENSP00000309052.5	Q8NEC5
	CATSPER1	ENST00000529244.1	TSL:3	n.442-8A>G		splice_region intron	N/A
	ENSG00000295293	ENST00000729053.1		n.250+258T>C		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.00000608 AC: 1 AN: 164388 Hom.: 0 Cov.: 0 AF XY: 0.0000105 AC XY: 1 AN XY: 95038

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 4034

American (AMR) AF: 0.00 AC: 0 AN: 10946

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5536

East Asian (EAS) AF: 0.00 AC: 0 AN: 5414

South Asian (SAS) AF: 0.00 AC: 0 AN: 28752

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 14170

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 528

European-Non Finnish (NFE) AF: 0.0000113 AC: 1 AN: 88352

Other (OTH) AF: 0.00 AC: 0 AN: 6656

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.18
DANN	Benign	0.36
PhyloP100		-3.1

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000070
dbscSNV1_RF	Benign	0.0
SpliceAI score (max)		0.090		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: rs1326391621; hg19: chr11-65784653;