Variant 8-100165607-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_003114.5(SPAG1):c.141-207C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0151 in 492,668 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.013 ( 20 hom., cov: 32)

Exomes 𝑓: 0.016 ( 64 hom. )

Consequence

SPAG1
NM_003114.5 intron

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.238

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 8-100165607-C-T is Benign according to our data. Variant chr8-100165607-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1212647.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0129 (1967/152216) while in subpopulation NFE AF= 0.023 (1564/68002). AF 95% confidence interval is 0.0221. There are 20 homozygotes in gnomad4. There are 891 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 20 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPAG1	NM_003114.5 linkuse as main transcript	c.141-207C>T		intron_variant		ENST00000388798.7

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
SPAG1	ENST00000388798.7 linkuse as main transcript	c.141-207C>T	intron_variant	1	NM_003114.5	P1	Q07617-1
SPAG1	ENST00000251809.4 linkuse as main transcript	c.141-207C>T	intron_variant	5		P1	Q07617-1
SPAG1	ENST00000520508.5 linkuse as main transcript	c.141-207C>T	intron_variant	5			Q07617-2
SPAG1	ENST00000520643.5 linkuse as main transcript	c.141-207C>T	intron_variant	2			Q07617-2

Frequencies

GnomAD3 genomes

AF:

0.0129

AC:

1967

AN:

152098

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00396

Gnomad AMI

AF:

0.0220

Gnomad AMR

AF:

0.00478

Gnomad ASJ

AF:

0.00950

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.00745

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0230

Gnomad OTH

AF:

0.00957

GnomAD4 exome

AF:

0.0160

AC:

5457

AN:

340452

Hom.:

AF XY:

0.0153

AC XY:

2730

AN XY:

178316

show subpopulations

Gnomad4 AFR exome

AF:

0.00407

Gnomad4 AMR exome

AF:

0.00584

Gnomad4 ASJ exome

AF:

0.00718

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00332

Gnomad4 FIN exome

AF:

0.00799

Gnomad4 NFE exome

AF:

0.0221

Gnomad4 OTH exome

AF:

0.0149

GnomAD4 genome

AF:

0.0129

AC:

1967

AN:

152216

Hom.:

Cov.:

AF XY:

0.0120

AC XY:

891

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00395

Gnomad4 AMR

AF:

0.00477

Gnomad4 ASJ

AF:

0.00950

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00270

Gnomad4 FIN

AF:

0.00745

Gnomad4 NFE

AF:

0.0230

Gnomad4 OTH

AF:

0.00947

Alfa

AF:

0.0153

Hom.:

Bravo

AF:

0.0125

Asia WGS

AF:

0.00115

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 16, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

8.0

DANN

Benign

0.74

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over