rs2248767

Variant names:

• chr8-100165538-C-T
• rs2248767
• NM_003114.5:c.141-276C>T

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.141-276C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.363 in 371,314 control chromosomes in the GnomAD database, including 25,510 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (10978 hom., cov: 32)
  • Exomes 𝑓: 0.35 (14532 hom.)
• Consequence: SPAG1 NM_003114.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0350
• Publications: 2 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]

UFM1P3 (HGNC:55148): (UFM1 pseudogene 3)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 8-100165538-C-T is Benign according to our data. Variant chr8-100165538-C-T is described in ClinVar as Benign. ClinVar VariationId is 1259217.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003114.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG1	NM_003114.5	MANE Select	c.141-276C>T		intron	N/A	NP_003105.2
	SPAG1	NM_001374321.1		c.141-276C>T		intron	N/A	NP_001361250.1	Q07617-1
	SPAG1	NM_172218.3		c.141-276C>T		intron	N/A	NP_757367.1	Q07617-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPAG1	ENST00000388798.7	TSL:1 MANE Select	c.141-276C>T		intron	N/A	ENSP00000373450.3	Q07617-1
	SPAG1	ENST00000251809.4	TSL:5	c.141-276C>T		intron	N/A	ENSP00000251809.3	Q07617-1
	SPAG1	ENST00000964470.1		c.141-276C>T		intron	N/A	ENSP00000634529.1

Frequencies

GnomAD3 genomes AF: 0.377 AC: 57094 AN: 151600 Hom.: 10970 Cov.: 32

Gnomad AFR AF: 0.390

Gnomad AMI AF: 0.352

Gnomad AMR AF: 0.468

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.510

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.353 AC: 77557 AN: 219598 Hom.: 14532 AF XY: 0.348 AC XY: 41223 AN XY: 118444

African (AFR) AF: 0.390 AC: 2348 AN: 6024

American (AMR) AF: 0.475 AC: 3871 AN: 8158

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 2146 AN: 6496

East Asian (EAS) AF: 0.499 AC: 5757 AN: 11538

South Asian (SAS) AF: 0.294 AC: 9222 AN: 31412

European-Finnish (FIN) AF: 0.331 AC: 3247 AN: 9800

Middle Eastern (MID) AF: 0.281 AC: 264 AN: 938

European-Non Finnish (NFE) AF: 0.349 AC: 46331 AN: 132904

Other (OTH) AF: 0.355 AC: 4371 AN: 12328

GnomAD4 genome AF: 0.377 AC: 57124 AN: 151716 Hom.: 10978 Cov.: 32 AF XY: 0.376 AC XY: 27895 AN XY: 74140

African (AFR) AF: 0.390 AC: 16111 AN: 41322

American (AMR) AF: 0.468 AC: 7138 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1202 AN: 3468

East Asian (EAS) AF: 0.511 AC: 2622 AN: 5134

South Asian (SAS) AF: 0.302 AC: 1455 AN: 4818

European-Finnish (FIN) AF: 0.330 AC: 3487 AN: 10552

Middle Eastern (MID) AF: 0.353 AC: 103 AN: 292

European-Non Finnish (NFE) AF: 0.352 AC: 23924 AN: 67870

Other (OTH) AF: 0.362 AC: 763 AN: 2110

Alfa AF: 0.358 Hom.: 3380

Bravo AF: 0.392

Asia WGS AF: 0.405 AC: 1408 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.8
DANN	Benign	0.51
PhyloP100		-0.035
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: rs2248767; hg19: chr8-101177766;