8-100165529-C-G

Variant names:

• chr8-100165529-C-G
• rs2248768
• NM_003114.5:c.141-285C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003114.5(SPAG1):​c.141-285C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000811 in 369,726 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000092 (0 hom.)
• Consequence: SPAG1 NM_003114.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.976
• Publications: 2 publications found

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]

UFM1P3 (HGNC:55148): (UFM1 pseudogene 3)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003114.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG1	NM_003114.5	MANE Select	c.141-285C>G		intron	N/A	NP_003105.2
	SPAG1	NM_001374321.1		c.141-285C>G		intron	N/A	NP_001361250.1	Q07617-1
	SPAG1	NM_172218.3		c.141-285C>G		intron	N/A	NP_757367.1	Q07617-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG1	ENST00000388798.7	TSL:1 MANE Select	c.141-285C>G		intron	N/A	ENSP00000373450.3	Q07617-1
	SPAG1	ENST00000251809.4	TSL:5	c.141-285C>G		intron	N/A	ENSP00000251809.3	Q07617-1
	SPAG1	ENST00000964470.1		c.141-285C>G		intron	N/A	ENSP00000634529.1

Frequencies

GnomAD3 genomes AF: 0.00000659 AC: 1 AN: 151724 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000917 AC: 2 AN: 218002 Hom.: 0 AF XY: 0.0000170 AC XY: 2 AN XY: 117954

African (AFR) AF: 0.00 AC: 0 AN: 5916

American (AMR) AF: 0.00 AC: 0 AN: 8270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6296

East Asian (EAS) AF: 0.00 AC: 0 AN: 11096

South Asian (SAS) AF: 0.00 AC: 0 AN: 32444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9766

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 890

European-Non Finnish (NFE) AF: 0.0000152 AC: 2 AN: 131244

Other (OTH) AF: 0.00 AC: 0 AN: 12080

GnomAD4 genome AF: 0.00000659 AC: 1 AN: 151724 Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1 AN XY: 74082

African (AFR) AF: 0.00 AC: 0 AN: 41248

American (AMR) AF: 0.00 AC: 0 AN: 15230

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5158

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10560

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67916

Other (OTH) AF: 0.00 AC: 0 AN: 2090

Alfa AF: 0.00 Hom.: 518

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.55
DANN	Benign	0.30
PhyloP100		-0.98

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: rs2248768; hg19: chr8-101177757;