8-100213262-TGCG-TGCGGCGGCG

Variant names:

• chr8-100213262-T-TGCGGCG
• rs962670800
• NM_003114.5:c.1280_1285dupCGGCGG

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM4

The NM_003114.5(SPAG1):​c.1280_1285dupCGGCGG​(p.Ala427_Ala428dup) variant causes a disruptive inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000019 in 1,213,158 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: SPAG1 NM_003114.5 disruptive_inframe_insertion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.672

Genes affected

SPAG1 (HGNC:11212): (sperm associated antigen 1) 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 agglutinating antibodies from an infertile woman. Furthermore, immunization of female rats with the recombinant human protein reduced fertility. This protein localizes to the plasma membrane of germ cells in the testis and to the post-acrosomal plasma membrane of mature spermatozoa. Recombinant polypeptide binds GTP and exhibits GTPase activity. Thus, this protein may regulate GTP signal transduction pathways involved in spermatogenesis and fertilization. Two transcript variants of this gene encode the same protein. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM4: Nonframeshift variant in NON repetitive region in NM_003114.5.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG1	NM_003114.5	c.1280_1285dupCGGCGG	p.Ala427_Ala428dup	disruptive_inframe_insertion	Exon 11 of 19	ENST00000388798.7	NP_003105.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG1	ENST00000388798.7	c.1280_1285dupCGGCGG	p.Ala427_Ala428dup	disruptive_inframe_insertion	Exon 11 of 19	1	NM_003114.5	ENSP00000373450.3
SPAG1	ENST00000251809.4	c.1280_1285dupCGGCGG	p.Ala427_Ala428dup	disruptive_inframe_insertion	Exon 11 of 19	5		ENSP00000251809.3
SPAG1	ENST00000523302.1	n.187_192dupCGGCGG		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes AF: 0.0000402 AC: 6 AN: 149410 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000298

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000160 AC: 17 AN: 1063646 Hom.: 0 Cov.: 32 AF XY: 0.0000257 AC XY: 13 AN XY: 505802

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000508

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000165

Gnomad4 OTH exome AF: 0.0000239

GnomAD4 genome AF: 0.0000401 AC: 6 AN: 149512 Hom.: 0 Cov.: 33 AF XY: 0.0000411 AC XY: 3 AN XY: 73018

Gnomad4 AFR AF: 0.0000243

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000622

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000298

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs962670800; hg19: chr8-101225490;