8-100162715-C-T

Variant names:

• chr8-100162715-C-T
• rs56321830
• NM_003114.5:c.140+295C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003114.5(SPAG1):​c.140+295C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.167 in 152,090 control chromosomes in the GnomAD database, including 2,235 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.17 (2235 hom., cov: 32)
• Consequence: SPAG1 NM_003114.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.60
• Publications: 1 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]

SPAG1 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 28

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, PanelApp Australia, ClinGen
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BP6: Variant 8-100162715-C-T is Benign according to our data. Variant chr8-100162715-C-T is described in ClinVar as Benign. ClinVar VariationId is 1181021.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.203 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.140+295C>T		intron	N/A	NP_003105.2
	SPAG1	NM_001374321.1		c.140+295C>T		intron	N/A	NP_001361250.1	Q07617-1
	SPAG1	NM_172218.3		c.140+295C>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.140+295C>T		intron	N/A	ENSP00000373450.3	Q07617-1
	SPAG1	ENST00000251809.4	TSL:5	c.140+295C>T		intron	N/A	ENSP00000251809.3	Q07617-1
	SPAG1	ENST00000964470.1		c.140+295C>T		intron	N/A	ENSP00000634529.1

Frequencies

GnomAD3 genomes AF: 0.167 AC: 25383 AN: 151972 Hom.: 2237 Cov.: 32

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.198

Gnomad EAS AF: 0.0716

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.180

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.167 AC: 25389 AN: 152090 Hom.: 2235 Cov.: 32 AF XY: 0.168 AC XY: 12471 AN XY: 74360

African (AFR) AF: 0.117 AC: 4873 AN: 41480

American (AMR) AF: 0.171 AC: 2621 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.198 AC: 688 AN: 3468

East Asian (EAS) AF: 0.0716 AC: 370 AN: 5170

South Asian (SAS) AF: 0.214 AC: 1030 AN: 4822

European-Finnish (FIN) AF: 0.231 AC: 2439 AN: 10566

Middle Eastern (MID) AF: 0.173 AC: 51 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12856 AN: 67982

Other (OTH) AF: 0.177 AC: 374 AN: 2108

Alfa AF: 0.185 Hom.: 349

Bravo AF: 0.159

Asia WGS AF: 0.141 AC: 491 AN: 3478

ClinVar

ClinVar submissions

Significance: 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	-1.0
CADD	Benign	0.78
DANN	Benign	0.31
PhyloP100		-1.6
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: rs56321830; hg19: chr8-101174943;