10-22356057-T-G

Variant names:

• chr10-22356057-T-G
• rs3952313
• NM_012443.4:c.122-8796T>G

Variant summary

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

The NM_012443.4(SPAG6):​c.122-8796T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,236 control chromosomes in the GnomAD database, including 55,113 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 0.85 (55113 hom., cov: 32)
• Consequence: SPAG6 NM_012443.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.249
• Publications: 6 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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.948 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG6	NM_012443.4	c.122-8796T>G		intron_variant	Intron 2 of 10	ENST00000376624.8	NP_036575.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG6	ENST00000376624.8	c.122-8796T>G		intron_variant	Intron 2 of 10	1	NM_012443.4	ENSP00000365811.3

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128829 AN: 152118 Hom.: 55053 Cov.: 32

Gnomad AFR AF: 0.956

Gnomad AMI AF: 0.555

Gnomad AMR AF: 0.782

Gnomad ASJ AF: 0.829

Gnomad EAS AF: 0.785

Gnomad SAS AF: 0.845

Gnomad FIN AF: 0.864

Gnomad MID AF: 0.870

Gnomad NFE AF: 0.802

Gnomad OTH AF: 0.840

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

GnomAD4 genome AF: 0.847 AC: 128937 AN: 152236 Hom.: 55113 Cov.: 32 AF XY: 0.846 AC XY: 62987 AN XY: 74436

African (AFR) AF: 0.956 AC: 39713 AN: 41542

American (AMR) AF: 0.781 AC: 11941 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.829 AC: 2879 AN: 3472

East Asian (EAS) AF: 0.785 AC: 4066 AN: 5180

South Asian (SAS) AF: 0.844 AC: 4076 AN: 4828

European-Finnish (FIN) AF: 0.864 AC: 9152 AN: 10598

Middle Eastern (MID) AF: 0.884 AC: 260 AN: 294

European-Non Finnish (NFE) AF: 0.802 AC: 54567 AN: 68008

Other (OTH) AF: 0.841 AC: 1777 AN: 2114

Alfa AF: 0.834 Hom.: 41920

Bravo AF: 0.844

Asia WGS AF: 0.793 AC: 2758 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.2
DANN	Benign	0.55
PhyloP100		-0.25
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs3952313; hg19: chr10-22644986;