NM_003114.5:c.141-285C>A

Variant names:

• chr8-100165529-C-A
• rs2248768
• NM_003114.5:c.141-285C>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.141-285C>A 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 369,032 control chromosomes in the GnomAD database, including 25,300 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (10981 hom., cov: 32)
  • Exomes 𝑓: 0.35 (14319 hom.)
• Consequence: SPAG1 NM_003114.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.976
• 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=-0.91).
• BP6: Variant 8-100165529-C-A is Benign according to our data. Variant chr8-100165529-C-A is described in ClinVar as Benign. ClinVar VariationId is 1239077.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.141-285C>A		intron	N/A	NP_003105.2
	SPAG1	NM_001374321.1		c.141-285C>A		intron	N/A	NP_001361250.1	Q07617-1
	SPAG1	NM_172218.3		c.141-285C>A		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.141-285C>A		intron	N/A	ENSP00000373450.3	Q07617-1
	SPAG1	ENST00000251809.4	TSL:5	c.141-285C>A		intron	N/A	ENSP00000251809.3	Q07617-1
	SPAG1	ENST00000964470.1		c.141-285C>A		intron	N/A	ENSP00000634529.1

Frequencies

GnomAD3 genomes AF: 0.376 AC: 57098 AN: 151660 Hom.: 10973 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: 0.299

Gnomad FIN AF: 0.331

Gnomad MID AF: 0.360

Gnomad NFE AF: 0.353

Gnomad OTH AF: 0.362

GnomAD4 exome AF: 0.353 AC: 76714 AN: 217254 Hom.: 14319 AF XY: 0.347 AC XY: 40825 AN XY: 117566

African (AFR) AF: 0.386 AC: 2276 AN: 5894

American (AMR) AF: 0.473 AC: 3903 AN: 8244

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 2055 AN: 6274

East Asian (EAS) AF: 0.499 AC: 5515 AN: 11056

South Asian (SAS) AF: 0.294 AC: 9500 AN: 32354

European-Finnish (FIN) AF: 0.331 AC: 3222 AN: 9744

Middle Eastern (MID) AF: 0.286 AC: 254 AN: 888

European-Non Finnish (NFE) AF: 0.350 AC: 45716 AN: 130776

Other (OTH) AF: 0.355 AC: 4273 AN: 12024

GnomAD4 genome AF: 0.376 AC: 57129 AN: 151778 Hom.: 10981 Cov.: 32 AF XY: 0.376 AC XY: 27907 AN XY: 74180

African (AFR) AF: 0.390 AC: 16116 AN: 41346

American (AMR) AF: 0.468 AC: 7138 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1203 AN: 3470

East Asian (EAS) AF: 0.510 AC: 2625 AN: 5144

South Asian (SAS) AF: 0.299 AC: 1441 AN: 4814

European-Finnish (FIN) AF: 0.331 AC: 3490 AN: 10556

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

European-Non Finnish (NFE) AF: 0.352 AC: 23930 AN: 67894

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

Alfa AF: 0.230 Hom.: 518

Bravo AF: 0.392

Asia WGS AF: 0.404 AC: 1406 AN: 3478

ClinVar

ClinVar submissions

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	-0.91
CADD	Benign	0.54
DANN	Benign	0.55
PhyloP100		-0.98
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: rs2248768; hg19: chr8-101177757;