rs1788190

Variant names:

• chr8-100240956-G-A
• rs1788190
• NM_003114.5:c.2715G>A

Your query was ambiguous. Multiple possible variants found:

• chr8-100240956-G-A
• chr8-100240956-G-C
• chr8-100240956-G-T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_003114.5(SPAG1):​c.2715G>A​(p.Ser905Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.352 in 1,611,486 control chromosomes in the GnomAD database, including 104,519 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (7844 hom., cov: 30)
  • Exomes 𝑓: 0.36 (96675 hom.)
• Consequence: SPAG1 NM_003114.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.649
• Publications: 26 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), ClinGen, PanelApp Australia, G2P
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 8-100240956-G-A is Benign according to our data. Variant chr8-100240956-G-A is described in ClinVar as Benign. ClinVar VariationId is 262803.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.649 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.479 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG1	NM_003114.5	c.2715G>A	p.Ser905Ser	synonymous_variant	Exon 19 of 19	ENST00000388798.7	NP_003105.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG1	ENST00000388798.7	c.2715G>A	p.Ser905Ser	synonymous_variant	Exon 19 of 19	1	NM_003114.5	ENSP00000373450.3
SPAG1	ENST00000251809.4	c.2715G>A	p.Ser905Ser	synonymous_variant	Exon 19 of 19	5		ENSP00000251809.3
SPAG1	ENST00000519409.1	n.213+185G>A		intron_variant	Intron 1 of 1	3

Frequencies

GnomAD3 genomes AF: 0.293 AC: 44144 AN: 150532 Hom.: 7841 Cov.: 30

Gnomad AFR AF: 0.0809

Gnomad AMI AF: 0.464

Gnomad AMR AF: 0.426

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.297

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.326

Gnomad NFE AF: 0.364

Gnomad OTH AF: 0.300

GnomAD2 exomes AF: 0.363 AC: 90876 AN: 250508 AF XY: 0.360

Gnomad AFR exome AF: 0.0725

Gnomad AMR exome AF: 0.490

Gnomad ASJ exome AF: 0.340

Gnomad EAS exome AF: 0.485

Gnomad FIN exome AF: 0.339

Gnomad NFE exome AF: 0.370

Gnomad OTH exome AF: 0.350

GnomAD4 exome AF: 0.358 AC: 523517 AN: 1460846 Hom.: 96675 Cov.: 36 AF XY: 0.357 AC XY: 259431 AN XY: 726734

African (AFR) AF: 0.0708 AC: 2368 AN: 33456

American (AMR) AF: 0.479 AC: 21356 AN: 44608

Ashkenazi Jewish (ASJ) AF: 0.339 AC: 8857 AN: 26100

East Asian (EAS) AF: 0.490 AC: 19434 AN: 39630

South Asian (SAS) AF: 0.299 AC: 25751 AN: 86140

European-Finnish (FIN) AF: 0.330 AC: 17620 AN: 53400

Middle Eastern (MID) AF: 0.338 AC: 1949 AN: 5764

European-Non Finnish (NFE) AF: 0.365 AC: 405484 AN: 1111406

Other (OTH) AF: 0.343 AC: 20698 AN: 60342

GnomAD4 genome AF: 0.293 AC: 44153 AN: 150640 Hom.: 7844 Cov.: 30 AF XY: 0.297 AC XY: 21850 AN XY: 73530

African (AFR) AF: 0.0809 AC: 3310 AN: 40938

American (AMR) AF: 0.426 AC: 6459 AN: 15158

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1199 AN: 3458

East Asian (EAS) AF: 0.496 AC: 2543 AN: 5132

South Asian (SAS) AF: 0.299 AC: 1423 AN: 4764

European-Finnish (FIN) AF: 0.340 AC: 3460 AN: 10178

Middle Eastern (MID) AF: 0.315 AC: 90 AN: 286

European-Non Finnish (NFE) AF: 0.364 AC: 24616 AN: 67714

Other (OTH) AF: 0.300 AC: 630 AN: 2100

Alfa AF: 0.331 Hom.: 20933

Bravo AF: 0.291

Asia WGS AF: 0.362 AC: 1256 AN: 3474

EpiCase AF: 0.358

EpiControl AF: 0.363

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Primary ciliary dyskinesia 28 Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 17, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia Benign:1

Jul 07, 2016

Ambry Genetics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.1
DANN	Benign	0.37
PhyloP100		-0.65
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: rs1788190; hg19: chr8-101253184; COSMIC: COSV52557780; COSMIC: COSV52557780;