8-100165766-G-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003114.5(SPAG1):c.141-48G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00108 in 1,526,144 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0058 (11 hom., cov: 32)
  • Exomes 𝑓: 0.00056 (6 hom.)
• Consequence: SPAG1 NM_003114.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.71

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 8-100165766-G-T is Benign according to our data. Variant chr8-100165766-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 1300843.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0058 (883/152286) while in subpopulation AFR AF= 0.02 (831/41532). AF 95% confidence interval is 0.0189. There are 11 homozygotes in gnomad4. There are 404 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPAG1	NM_003114.5	c.141-48G>T		intron_variant		ENST00000388798.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPAG1	ENST00000388798.7	c.141-48G>T		intron_variant		1	NM_003114.5	P1
SPAG1	ENST00000251809.4	c.141-48G>T		intron_variant		5		P1
SPAG1	ENST00000520508.5	c.141-48G>T		intron_variant		5
SPAG1	ENST00000520643.5	c.141-48G>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.00582 AC: 885 AN: 152168 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.0201

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000235

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00150 AC: 329 AN: 219042 Hom.: 2 AF XY: 0.00111 AC XY: 131 AN XY: 118418

Gnomad AFR exome AF: 0.0192

Gnomad AMR exome AF: 0.00115

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000593

Gnomad OTH exome AF: 0.000967

GnomAD4 exome AF: 0.000557 AC: 765 AN: 1373858 Hom.: 6 Cov.: 20 AF XY: 0.000480 AC XY: 328 AN XY: 683662

Gnomad4 AFR exome AF: 0.0171

Gnomad4 AMR exome AF: 0.00133

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000256

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000867

Gnomad4 OTH exome AF: 0.00151

GnomAD4 genome AF: 0.00580 AC: 883 AN: 152286 Hom.: 11 Cov.: 32 AF XY: 0.00543 AC XY: 404 AN XY: 74462

Gnomad4 AFR AF: 0.0200

Gnomad4 AMR AF: 0.00196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000235

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00278 Hom.: 1

Bravo AF: 0.00645

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Apr 06, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	0.27
Dann	Benign	0.76

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

Publications

LitVar

Other links and lift over

dbSNP: rs76197337; hg19: chr8-101177994;