rs74370304

Variant names:

• chr8-100165607-C-T
• rs74370304
• NM_003114.5:c.141-207C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.238
• Publications: 0 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 -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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR,AD gene

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.141-207C>T		intron	N/A	NP_003105.2
	SPAG1	NM_001374321.1		c.141-207C>T		intron	N/A	NP_001361250.1	Q07617-1
	SPAG1	NM_172218.3		c.141-207C>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.141-207C>T		intron	N/A	ENSP00000373450.3	Q07617-1
	SPAG1	ENST00000251809.4	TSL:5	c.141-207C>T		intron	N/A	ENSP00000251809.3	Q07617-1
	SPAG1	ENST00000964470.1		c.141-207C>T		intron	N/A	ENSP00000634529.1

Frequencies

GnomAD3 genomes AF: 0.0129 AC: 1967 AN: 152098 Hom.: 20 Cov.: 32

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.: 64 AF XY: 0.0153 AC XY: 2730 AN XY: 178316

African (AFR) AF: 0.00407 AC: 38 AN: 9346

American (AMR) AF: 0.00584 AC: 66 AN: 11310

Ashkenazi Jewish (ASJ) AF: 0.00718 AC: 79 AN: 11002

East Asian (EAS) AF: 0.00 AC: 0 AN: 23586

South Asian (SAS) AF: 0.00332 AC: 93 AN: 28022

European-Finnish (FIN) AF: 0.00799 AC: 185 AN: 23168

Middle Eastern (MID) AF: 0.000624 AC: 1 AN: 1602

European-Non Finnish (NFE) AF: 0.0221 AC: 4692 AN: 212060

Other (OTH) AF: 0.0149 AC: 303 AN: 20356

GnomAD4 genome AF: 0.0129 AC: 1967 AN: 152216 Hom.: 20 Cov.: 32 AF XY: 0.0120 AC XY: 891 AN XY: 74418

African (AFR) AF: 0.00395 AC: 164 AN: 41532

American (AMR) AF: 0.00477 AC: 73 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.00950 AC: 33 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4814

European-Finnish (FIN) AF: 0.00745 AC: 79 AN: 10600

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0230 AC: 1564 AN: 68002

Other (OTH) AF: 0.00947 AC: 20 AN: 2112

Alfa AF: 0.0202 Hom.: 58

Bravo AF: 0.0125

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.0
DANN	Benign	0.74
PhyloP100		0.24
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs74370304; hg19: chr8-101177835;