10-22386927-CAG-AGA

Variant names:

• chr10-22386927-CAG-AGA
• NM_012443.4:c.646_648delCAGinsAGA
• SPAG6 p.Gln216Arg

Variant summary

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

The NM_012443.4(SPAG6):​c.646_648delCAGinsAGA​(p.Gln216Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, 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: not found (cov: 32)
• Consequence: SPAG6 NM_012443.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.73
• Publications: 0 publications found

Genes affected

SPAG6 (HGNC:11215): (sperm associated antigen 6) The correlation of anti-sperm antibodies with cases of unexplained infertility implicates a role for these antibodies in blocking fertilization. Improved diagnosis and treatment of immunologic infertility, as well as identification of proteins for targeted contraception, are dependent on the identification and characterization of relevant sperm antigens. The protein expressed by this gene is recognized by anti-sperm antibodies from an infertile man. This protein localizes to the tail of permeabilized human sperm and contains eight contiguous armadillo repeats, a motif known to mediate protein-protein interactions. Studies in mice suggest that this protein is involved in sperm flagellar motility and maintenance of the structural integrity of mature sperm. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2011]

ENSG00000233451 (HGNC:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012443.4. 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
	SPAG6	NM_012443.4	MANE Select	c.646_648delCAGinsAGA	p.Gln216Arg	missense	N/A	NP_036575.1	A0A140VJU9
	SPAG6	NM_001253854.2		c.571_573delCAGinsAGA	p.Gln191Arg	missense	N/A	NP_001240783.1	O75602-5
	SPAG6	NM_001253855.2		c.580_582delCAGinsAGA	p.Gln194Arg	missense	N/A	NP_001240784.1	A0A0A0MRT8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG6	ENST00000376624.8	TSL:1 MANE Select	c.646_648delCAGinsAGA	p.Gln216Arg	missense	N/A	ENSP00000365811.3	O75602-1
	SPAG6	ENST00000376603.6	TSL:1	c.580_582delCAGinsAGA	p.Gln194Arg	missense	N/A	ENSP00000365788.3	A0A0A0MRT8
	SPAG6	ENST00000313311.10	TSL:1	c.646_648delCAGinsAGA	p.Gln216Arg	missense	N/A	ENSP00000323599.6	O75602-2

Frequencies

GnomAD3 genomes Cov.: 32

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.7

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr10-22675856;