ENST00000487973.1:n.234-4658G>C

Variant names:

• chr10-22444067-G-C
• rs16922285
• ENST00000487973.1:n.234-4658G>C

Variant summary

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

The ENST00000487973.1(SPAG6):​n.234-4658G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.145 in 152,054 control chromosomes in the GnomAD database, including 5,272 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 (5272 hom., cov: 32)
• Consequence: SPAG6 ENST00000487973.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.639
• 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.492 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105376449	XR_001747392.2	n.78-4658G>C		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG6	ENST00000487973.1	n.234-4658G>C		intron_variant	Intron 2 of 3	5
ENSG00000286810	ENST00000652874.1	n.60-2573C>G		intron_variant	Intron 1 of 1
ENSG00000286810	ENST00000658386.1	n.151-2573C>G		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21906 AN: 151936 Hom.: 5247 Cov.: 32

Gnomad AFR AF: 0.498

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0557

Gnomad ASJ AF: 0.00693

Gnomad EAS AF: 0.0108

Gnomad SAS AF: 0.00519

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00250

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.145 AC: 21975 AN: 152054 Hom.: 5272 Cov.: 32 AF XY: 0.139 AC XY: 10308 AN XY: 74346

African (AFR) AF: 0.498 AC: 20639 AN: 41428

American (AMR) AF: 0.0555 AC: 847 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00693 AC: 24 AN: 3462

East Asian (EAS) AF: 0.0108 AC: 56 AN: 5176

South Asian (SAS) AF: 0.00478 AC: 23 AN: 4816

European-Finnish (FIN) AF: 0.0000945 AC: 1 AN: 10584

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

European-Non Finnish (NFE) AF: 0.00250 AC: 170 AN: 67994

Other (OTH) AF: 0.0989 AC: 209 AN: 2114

Alfa AF: 0.00737 Hom.: 20

Bravo AF: 0.165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.62
DANN	Benign	0.65
PhyloP100		-0.64

Splicing

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

Other links and lift over

dbSNP: rs16922285; hg19: chr10-22732996;