chr8-100162198-G-C

Variant names:

• chr8-100162198-G-C
• rs16898015
• NM_003114.5:c.-2-81G>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003114.5(SPAG1):​c.-2-81G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000601 in 998,410 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000060 (0 hom.)
• Consequence: SPAG1 NM_003114.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 0 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]

SPAG1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 28

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).

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.-2-81G>C		intron	N/A	NP_003105.2
	SPAG1	NM_001374321.1		c.-2-81G>C		intron	N/A	NP_001361250.1	Q07617-1
	SPAG1	NM_172218.3		c.-2-81G>C		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.-2-81G>C		intron	N/A	ENSP00000373450.3	Q07617-1
	SPAG1	ENST00000251809.4	TSL:5	c.-2-81G>C		intron	N/A	ENSP00000251809.3	Q07617-1
	SPAG1	ENST00000964470.1		c.-2-81G>C		intron	N/A	ENSP00000634529.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000601 AC: 6 AN: 998410 Hom.: 0 AF XY: 0.00000594 AC XY: 3 AN XY: 505142

African (AFR) AF: 0.00 AC: 0 AN: 20332

American (AMR) AF: 0.00 AC: 0 AN: 18930

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20274

East Asian (EAS) AF: 0.00 AC: 0 AN: 30444

South Asian (SAS) AF: 0.00 AC: 0 AN: 61408

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47490

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3250

European-Non Finnish (NFE) AF: 0.00000797 AC: 6 AN: 752930

Other (OTH) AF: 0.00 AC: 0 AN: 43352

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	3.3
DANN	Benign	0.61
PhyloP100		-0.0050

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: rs16898015; hg19: chr8-101174426;