chr8-100162198-G-A

Variant names:

• chr8-100162198-G-A
• rs16898015
• NM_003114.5:c.-2-81G>A

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.-2-81G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,148,662 control chromosomes in the GnomAD database, including 24,104 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3673 hom., cov: 32)
  • Exomes 𝑓: 0.20 (20431 hom.)
• Consequence: SPAG1 NM_003114.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.00500

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 8-100162198-G-A is Benign according to our data. Variant chr8-100162198-G-A is described in ClinVar as [Benign]. Clinvar id is 1248919.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.262 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG1	NM_003114.5	c.-2-81G>A		intron_variant	Intron 1 of 18	ENST00000388798.7	NP_003105.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG1	ENST00000388798.7	c.-2-81G>A		intron_variant	Intron 1 of 18	1	NM_003114.5	ENSP00000373450.3
SPAG1	ENST00000251809.4	c.-2-81G>A		intron_variant	Intron 1 of 18	5		ENSP00000251809.3
SPAG1	ENST00000520508.5	c.-2-81G>A		intron_variant	Intron 1 of 9	5		ENSP00000428070.1
SPAG1	ENST00000520643.5	c.-2-81G>A		intron_variant	Intron 1 of 9	2		ENSP00000427716.1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32758 AN: 151936 Hom.: 3669 Cov.: 32

Gnomad AFR AF: 0.266

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.203

Gnomad EAS AF: 0.173

Gnomad SAS AF: 0.261

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.218

GnomAD4 exome AF: 0.199 AC: 198517 AN: 996608 Hom.: 20431 AF XY: 0.201 AC XY: 101161 AN XY: 504228

Gnomad4 AFR exome AF: 0.265 AC: 5377 AN: 20266

Gnomad4 AMR exome AF: 0.208 AC: 3930 AN: 18892

Gnomad4 ASJ exome AF: 0.195 AC: 3940 AN: 20250

Gnomad4 EAS exome AF: 0.203 AC: 6174 AN: 30414

Gnomad4 SAS exome AF: 0.278 AC: 17066 AN: 61288

Gnomad4 FIN exome AF: 0.239 AC: 11352 AN: 47450

Gnomad4 NFE exome AF: 0.188 AC: 141224 AN: 751534

Gnomad4 Remaining exome AF: 0.202 AC: 8743 AN: 43268

GnomAD4 genome AF: 0.216 AC: 32793 AN: 152054 Hom.: 3673 Cov.: 32 AF XY: 0.216 AC XY: 16090 AN XY: 74328

Gnomad4 AFR AF: 0.266 AC: 0.265851 AN: 0.265851

Gnomad4 AMR AF: 0.192 AC: 0.192383 AN: 0.192383

Gnomad4 ASJ AF: 0.203 AC: 0.203053 AN: 0.203053

Gnomad4 EAS AF: 0.173 AC: 0.172921 AN: 0.172921

Gnomad4 SAS AF: 0.260 AC: 0.260382 AN: 0.260382

Gnomad4 FIN AF: 0.231 AC: 0.231322 AN: 0.231322

Gnomad4 NFE AF: 0.190 AC: 0.190273 AN: 0.190273

Gnomad4 OTH AF: 0.217 AC: 0.217062 AN: 0.217062

Alfa AF: 0.190 Hom.: 4689

Bravo AF: 0.213

Asia WGS AF: 0.217 AC: 754 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Apr 20, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.7
DANN	Benign	0.41
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

Publications

LitVar

Other links and lift over

dbSNP: rs16898015; hg19: chr8-101174426; COSMIC: COSV52562085; COSMIC: COSV52562085;