ENST00000487973.1:n.234-3758A>G

Variant names:

• chr10-22444967-A-G
• rs11012996
• ENST00000487973.1:n.234-3758A>G

Variant summary

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

The ENST00000487973.1(SPAG6):​n.234-3758A>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 152,102 control chromosomes in the GnomAD database, including 5,218 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 (5218 hom., cov: 32)
• Consequence: SPAG6 ENST00000487973.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.49 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOC105376449	XR_001747392.2	n.78-3758A>G		intron_variant	Intron 1 of 3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG6	ENST00000487973.1	n.234-3758A>G		intron_variant	Intron 2 of 3	5
ENSG00000286810	ENST00000652874.1	n.60-3473T>C		intron_variant	Intron 1 of 1
ENSG00000286810	ENST00000658386.1	n.151-3473T>C		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.143 AC: 21790 AN: 151984 Hom.: 5194 Cov.: 32

Gnomad AFR AF: 0.496

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0553

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.0110

Gnomad SAS AF: 0.00518

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0158

Gnomad NFE AF: 0.00248

Gnomad OTH AF: 0.0992

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

GnomAD4 genome AF: 0.144 AC: 21857 AN: 152102 Hom.: 5218 Cov.: 32 AF XY: 0.138 AC XY: 10257 AN XY: 74380

African (AFR) AF: 0.496 AC: 20527 AN: 41394

American (AMR) AF: 0.0551 AC: 843 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5178

South Asian (SAS) AF: 0.00477 AC: 23 AN: 4822

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10612

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

European-Non Finnish (NFE) AF: 0.00248 AC: 169 AN: 68016

Other (OTH) AF: 0.0982 AC: 207 AN: 2108

Alfa AF: 0.133 Hom.: 506

Bravo AF: 0.164

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	2.4
DANN	Benign	0.58
PhyloP100		0.15

Splicing

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

Other links and lift over

dbSNP: rs11012996; hg19: chr10-22733896;