rs112884253

chr8-100220270-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003114.5(SPAG1):c.1536-9C>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00387 in 1,597,254 control chromosomes in the GnomAD database, including 188 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.020 (103 hom., cov: 33)
  • Exomes 𝑓: 0.0021 (85 hom.)
• Consequence: SPAG1 NM_003114.5 splice_polypyrimidine_tract, intron
• Scores: Splicing: ADA: 0.00006279
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.266

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]

LOC105375669 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 8-100220270-C-G is Benign according to our data. Variant chr8-100220270-C-G is described in ClinVar as [Benign]. Clinvar id is 416531.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0675 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPAG1	NM_003114.5	c.1536-9C>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000388798.7
LOC105375669	XR_928450.3	n.14G>C		non_coding_transcript_exon_variant	1/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPAG1	ENST00000388798.7	c.1536-9C>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_003114.5	P1
SPAG1	ENST00000251809.4	c.1536-9C>G		splice_polypyrimidine_tract_variant, intron_variant		5		P1
SPAG1	ENST00000523302.1	n.343-4903C>G		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.0202 AC: 3069 AN: 152140 Hom.: 101 Cov.: 33

Gnomad AFR AF: 0.0694

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00759

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.0129

GnomAD3 exomes AF: 0.00578 AC: 1352 AN: 233780 Hom.: 37 AF XY: 0.00432 AC XY: 547 AN XY: 126638

Gnomad AFR exome AF: 0.0715

Gnomad AMR exome AF: 0.00456

Gnomad ASJ exome AF: 0.00283

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000259

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000286

Gnomad OTH exome AF: 0.00357

GnomAD4 exome AF: 0.00214 AC: 3094 AN: 1444996 Hom.: 85 Cov.: 31 AF XY: 0.00187 AC XY: 1341 AN XY: 718814

Gnomad4 AFR exome AF: 0.0691

Gnomad4 AMR exome AF: 0.00541

Gnomad4 ASJ exome AF: 0.00247

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000277

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000219

Gnomad4 OTH exome AF: 0.00513

GnomAD4 genome AF: 0.0203 AC: 3085 AN: 152258 Hom.: 103 Cov.: 33 AF XY: 0.0195 AC XY: 1453 AN XY: 74446

Gnomad4 AFR AF: 0.0696

Gnomad4 AMR AF: 0.00758

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000618

Gnomad4 OTH AF: 0.0128

Alfa AF: 0.00640 Hom.: 8

Bravo AF: 0.0228

Asia WGS AF: 0.00779 AC: 27 AN: 3478

EpiCase AF: 0.000547

EpiControl AF: 0.000357

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Primary ciliary dyskinesia 28 Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Oct 14, 2023	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Oct 21, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	14
Dann	Benign	0.77

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000063
dbscSNV1_RF	Benign	0.052
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs112884253; hg19: chr8-101232498;