rs11012997

Variant names:

• chr10-22445159-A-G
• rs11012997
• ENST00000487973.1:n.234-3566A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000487973.1(SPAG6):​n.234-3566A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 151,908 control chromosomes in the GnomAD database, including 5,222 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.14 (5222 hom., cov: 32)
• Consequence: SPAG6 ENST00000487973.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.578
• Publications: 2 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]

ENSG00000286810 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.491 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105376449	XR_001747392.2	n.78-3566A>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG6	ENST00000487973.1	n.234-3566A>G		intron_variant	Intron 2 of 3	5
ENSG00000286810	ENST00000652874.1	n.60-3665T>C		intron_variant	Intron 1 of 1
ENSG00000286810	ENST00000658386.1	n.151-3665T>C		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21795 AN: 151790 Hom.: 5198 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0548

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.0111

Gnomad SAS AF: 0.00520

Gnomad FIN AF: 0.0000946

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00249

Gnomad OTH AF: 0.0989

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

GnomAD4 genome AF: 0.144 AC: 21862 AN: 151908 Hom.: 5222 Cov.: 32 AF XY: 0.138 AC XY: 10272 AN XY: 74248

African (AFR) AF: 0.496 AC: 20542 AN: 41382

American (AMR) AF: 0.0546 AC: 834 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3468

East Asian (EAS) AF: 0.0111 AC: 57 AN: 5124

South Asian (SAS) AF: 0.00479 AC: 23 AN: 4806

European-Finnish (FIN) AF: 0.0000946 AC: 1 AN: 10576

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.00249 AC: 169 AN: 67976

Other (OTH) AF: 0.0979 AC: 206 AN: 2104

Alfa AF: 0.0594 Hom.: 2415

Bravo AF: 0.164

Asia WGS AF: 0.0440 AC: 153 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.1
DANN	Benign	0.46
PhyloP100		0.58

Splicing

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

Other links and lift over

dbSNP: rs11012997; hg19: chr10-22734088;