rs760624535

Variant names:

• chr8-100240747-C-T
• rs760624535
• NM_003114.5:c.2625C>T
• SPAG1 p.Tyr875Tyr

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_003114.5(SPAG1):​c.2625C>T​(p.Tyr875Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000103 in 1,453,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: SPAG1 NM_003114.5 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.284
• 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: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 8-100240747-C-T is Benign according to our data. Variant chr8-100240747-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 416528.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.284 with no splicing effect.

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.2625C>T	p.Tyr875Tyr	synonymous	Exon 18 of 19	NP_003105.2
	SPAG1	NM_001374321.1		c.2625C>T	p.Tyr875Tyr	synonymous	Exon 18 of 19	NP_001361250.1	Q07617-1
	SPAG1	NM_172218.3		c.2625C>T	p.Tyr875Tyr	synonymous	Exon 18 of 19	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.2625C>T	p.Tyr875Tyr	synonymous	Exon 18 of 19	ENSP00000373450.3	Q07617-1
	SPAG1	ENST00000251809.4	TSL:5	c.2625C>T	p.Tyr875Tyr	synonymous	Exon 18 of 19	ENSP00000251809.3	Q07617-1
	SPAG1	ENST00000964470.1		c.2625C>T	p.Tyr875Tyr	synonymous	Exon 18 of 19	ENSP00000634529.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000124 AC: 3 AN: 242906 AF XY: 0.00000761

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000270

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1453390 Hom.: 0 Cov.: 36 AF XY: 0.00000415 AC XY: 3 AN XY: 722738

African (AFR) AF: 0.00 AC: 0 AN: 32928

American (AMR) AF: 0.00 AC: 0 AN: 42924

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25650

East Asian (EAS) AF: 0.00 AC: 0 AN: 39664

South Asian (SAS) AF: 0.0000119 AC: 1 AN: 84322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53196

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.0000126 AC: 14 AN: 1109022

Other (OTH) AF: 0.00 AC: 0 AN: 59988

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Primary ciliary dyskinesia 28 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	1.8
DANN	Benign	0.25
PhyloP100		0.28

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs760624535;

hg19: chr8-101252975;