11-64304830-CGTGACCTTCATTCGGTCACCGCA-CGTGACCTTCATTCGGTCACCGCAGTGACCTTCATTCGGTCACCGCA

Variant names:

• chr11-64304830-C-CGTGACCTTCATTCGGTCACCGCA
• rs3217060
• NM_001039496.2:c.*184_*185insGTGACCTTCATTCGGTCACCGCA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001039496.2(CATSPERZ):​c.*184_*185insGTGACCTTCATTCGGTCACCGCA variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0308 in 544,704 control chromosomes in the GnomAD database, including 726 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type INS_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.050 (285 hom., cov: 32)
  • Exomes 𝑓: 0.023 (441 hom.)
• Consequence: CATSPERZ NM_001039496.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.922
• Publications: 1 publications found

Genes affected

CATSPERZ (HGNC:19231): (catsper channel auxiliary subunit zeta) Predicted to be involved in flagellated sperm motility; male meiotic nuclear division; and sperm capacitation. Located in cytoplasm and sperm principal piece. [provided by Alliance of Genome Resources, Apr 2022]

KCNK4-CATSPERZ (HGNC:56753): (KCNK4-CATSPERZ readthrough (NMD candidate)) This locus represents naturally occurring readthrough transcription between the neighboring KCNK4 (potassium channel subfamily K member 4) and the downstream TEX40 (testis expressed 40) chromosome 11. The readthrough transcript is a candidate for nonsense-mediated mRNA decay (NMD), and is unlikely to produce a protein product. [provided by RefSeq, Nov 2015]

ESRRA (HGNC:3471): (estrogen related receptor alpha) The protein encoded by this gene is a nuclear receptor that is most closely related to the estrogen receptor. This protein acts as a site-specific transcription factor and interacts with members of the PGC-1 family of transcription cofactors to regulate the expression of most genes involved in cellular energy production as well as in the process of mitochondrial biogenesis. A processed pseudogene of ESRRA is located on chromosome 13q12.1. [provided by RefSeq, Jun 2019]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0635 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001039496.2. 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
	CATSPERZ	NM_001039496.2	MANE Select	c.*184_*185insGTGACCTTCATTCGGTCACCGCA		downstream_gene	N/A	NP_001034585.1	Q9NTU4
	KCNK4-CATSPERZ	NR_133662.1		n.*61_*62insGTGACCTTCATTCGGTCACCGCA		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CATSPERZ	ENST00000328404.8	TSL:1 MANE Select	c.*184_*185insGTGACCTTCATTCGGTCACCGCA		downstream_gene	N/A	ENSP00000491717.1	Q9NTU4
	KCNK4-CATSPERZ	ENST00000539086.5	TSL:1	n.*61_*62insGTGACCTTCATTCGGTCACCGCA		downstream_gene	N/A
	ESRRA	ENST00000965463.1		c.-344_-343insGTGACCTTCATTCGGTCACCGCA		upstream_gene	N/A	ENSP00000635522.1

Frequencies

GnomAD3 genomes AF: 0.0502 AC: 7531 AN: 150004 Hom.: 285 Cov.: 32

Gnomad AFR AF: 0.0260

Gnomad AMI AF: 0.0805

Gnomad AMR AF: 0.0430

Gnomad ASJ AF: 0.0897

Gnomad EAS AF: 0.0553

Gnomad SAS AF: 0.0412

Gnomad FIN AF: 0.0423

Gnomad MID AF: 0.119

Gnomad NFE AF: 0.0652

Gnomad OTH AF: 0.0571

GnomAD4 exome AF: 0.0234 AC: 9226 AN: 394586 Hom.: 441 AF XY: 0.0232 AC XY: 4829 AN XY: 207766

African (AFR) AF: 0.0113 AC: 129 AN: 11380

American (AMR) AF: 0.0130 AC: 204 AN: 15640

Ashkenazi Jewish (ASJ) AF: 0.0437 AC: 517 AN: 11824

East Asian (EAS) AF: 0.0336 AC: 906 AN: 26964

South Asian (SAS) AF: 0.0145 AC: 561 AN: 38604

European-Finnish (FIN) AF: 0.0181 AC: 469 AN: 25920

Middle Eastern (MID) AF: 0.0401 AC: 75 AN: 1872

European-Non Finnish (NFE) AF: 0.0242 AC: 5784 AN: 239372

Other (OTH) AF: 0.0252 AC: 581 AN: 23010

GnomAD4 genome AF: 0.0502 AC: 7536 AN: 150118 Hom.: 285 Cov.: 32 AF XY: 0.0497 AC XY: 3647 AN XY: 73338

African (AFR) AF: 0.0261 AC: 1071 AN: 41076

American (AMR) AF: 0.0429 AC: 650 AN: 15162

Ashkenazi Jewish (ASJ) AF: 0.0897 AC: 308 AN: 3432

East Asian (EAS) AF: 0.0556 AC: 281 AN: 5054

South Asian (SAS) AF: 0.0410 AC: 193 AN: 4710

European-Finnish (FIN) AF: 0.0423 AC: 442 AN: 10438

Middle Eastern (MID) AF: 0.124 AC: 36 AN: 290

European-Non Finnish (NFE) AF: 0.0651 AC: 4363 AN: 66972

Other (OTH) AF: 0.0574 AC: 120 AN: 2090

Alfa AF: 0.0196 Hom.: 22

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.92
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3217060; hg19: chr11-64072302; COSMIC: COSV50005335;