rs3802149

Variant names:

• chr8-100191509-T-C
• rs3802149
• NM_003114.5:c.939+13T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003114.5(SPAG1):​c.939+13T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.2 in 1,548,334 control chromosomes in the GnomAD database, including 32,478 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (2456 hom., cov: 32)
  • Exomes 𝑓: 0.20 (30022 hom.)
• Consequence: SPAG1 NM_003114.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.127
• Publications: 8 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

ENSG00000302563 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 8-100191509-T-C is Benign according to our data. Variant chr8-100191509-T-C is described in ClinVar as Benign. ClinVar VariationId is 262804.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.217 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG1	NM_003114.5	c.939+13T>C		intron_variant	Intron 9 of 18	ENST00000388798.7	NP_003105.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG1	ENST00000388798.7	c.939+13T>C		intron_variant	Intron 9 of 18	1	NM_003114.5	ENSP00000373450.3

Frequencies

GnomAD3 genomes AF: 0.168 AC: 25513 AN: 152082 Hom.: 2459 Cov.: 32

Gnomad AFR AF: 0.0747

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.180

Gnomad ASJ AF: 0.228

Gnomad EAS AF: 0.0722

Gnomad SAS AF: 0.229

Gnomad FIN AF: 0.247

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.209

Gnomad OTH AF: 0.187

GnomAD2 exomes AF: 0.199 AC: 48737 AN: 245260 AF XY: 0.204

Gnomad AFR exome AF: 0.0716

Gnomad AMR exome AF: 0.217

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.0562

Gnomad FIN exome AF: 0.249

Gnomad NFE exome AF: 0.208

Gnomad OTH exome AF: 0.218

GnomAD4 exome AF: 0.203 AC: 283893 AN: 1396134 Hom.: 30022 Cov.: 22 AF XY: 0.205 AC XY: 142912 AN XY: 698032

African (AFR) AF: 0.0666 AC: 2125 AN: 31910

American (AMR) AF: 0.211 AC: 9189 AN: 43606

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 5812 AN: 25642

East Asian (EAS) AF: 0.0795 AC: 3131 AN: 39360

South Asian (SAS) AF: 0.247 AC: 20739 AN: 83824

European-Finnish (FIN) AF: 0.256 AC: 13605 AN: 53210

Middle Eastern (MID) AF: 0.243 AC: 1371 AN: 5638

European-Non Finnish (NFE) AF: 0.205 AC: 216283 AN: 1054668

Other (OTH) AF: 0.200 AC: 11638 AN: 58276

GnomAD4 genome AF: 0.168 AC: 25508 AN: 152200 Hom.: 2456 Cov.: 32 AF XY: 0.169 AC XY: 12589 AN XY: 74404

African (AFR) AF: 0.0747 AC: 3103 AN: 41552

American (AMR) AF: 0.180 AC: 2753 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.228 AC: 791 AN: 3470

East Asian (EAS) AF: 0.0722 AC: 374 AN: 5182

South Asian (SAS) AF: 0.228 AC: 1102 AN: 4830

European-Finnish (FIN) AF: 0.247 AC: 2610 AN: 10564

Middle Eastern (MID) AF: 0.221 AC: 65 AN: 294

European-Non Finnish (NFE) AF: 0.209 AC: 14189 AN: 68006

Other (OTH) AF: 0.185 AC: 389 AN: 2108

Alfa AF: 0.201 Hom.: 4408

Bravo AF: 0.157

Asia WGS AF: 0.150 AC: 522 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 27, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary ciliary dyskinesia 28 Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	7.0
DANN	Benign	0.65
PhyloP100		0.13
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: rs3802149; hg19: chr8-101203737;