chr11-66016827-C-T

Variant names:

• chr11-66016827-C-T
• rs955432976
• NM_053054.4:c.*63G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_053054.4(CATSPER1):​c.*63G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000707 in 1,414,406 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000071 (0 hom.)
• Consequence: CATSPER1 NM_053054.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.720
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).

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.*63G>A		3_prime_UTR	Exon 12 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.*63G>A		3_prime_UTR	Exon 12 of 12	ENSP00000309052.5	Q8NEC5
	CATSPER1	ENST00000529244.1	TSL:3	n.646G>A		non_coding_transcript_exon	Exon 6 of 6
	ENSG00000295293	ENST00000729053.1		n.153C>T		non_coding_transcript_exon	Exon 2 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000707 AC: 10 AN: 1414406 Hom.: 0 Cov.: 27 AF XY: 0.00000713 AC XY: 5 AN XY: 701070

African (AFR) AF: 0.00 AC: 0 AN: 32428

American (AMR) AF: 0.00 AC: 0 AN: 42186

Ashkenazi Jewish (ASJ) AF: 0.000251 AC: 6 AN: 23908

East Asian (EAS) AF: 0.00 AC: 0 AN: 39332

South Asian (SAS) AF: 0.00 AC: 0 AN: 80518

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52282

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5326

European-Non Finnish (NFE) AF: 0.00000185 AC: 2 AN: 1079936

Other (OTH) AF: 0.0000342 AC: 2 AN: 58490

GnomAD4 genome Cov.: 32

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	-	Spermatogenic failure 7 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.0
DANN	Benign	0.55
PhyloP100		0.72

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: rs955432976; hg19: chr11-65784298;