rs16898015

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr8-100162198-G-A
• chr8-100162198-G-C
• chr8-100162198-G-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.-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
• Publications: 7 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 -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 VariationId 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.

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.-2-81G>A		intron	N/A	NP_003105.2
	SPAG1	NM_001374321.1		c.-2-81G>A		intron	N/A	NP_001361250.1	Q07617-1
	SPAG1	NM_172218.3		c.-2-81G>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.-2-81G>A		intron	N/A	ENSP00000373450.3	Q07617-1
	SPAG1	ENST00000251809.4	TSL:5	c.-2-81G>A		intron	N/A	ENSP00000251809.3	Q07617-1
	SPAG1	ENST00000964470.1		c.-2-81G>A		intron	N/A	ENSP00000634529.1

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

African (AFR) AF: 0.265 AC: 5377 AN: 20266

American (AMR) AF: 0.208 AC: 3930 AN: 18892

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 3940 AN: 20250

East Asian (EAS) AF: 0.203 AC: 6174 AN: 30414

South Asian (SAS) AF: 0.278 AC: 17066 AN: 61288

European-Finnish (FIN) AF: 0.239 AC: 11352 AN: 47450

Middle Eastern (MID) AF: 0.219 AC: 711 AN: 3246

European-Non Finnish (NFE) AF: 0.188 AC: 141224 AN: 751534

Other (OTH) 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

African (AFR) AF: 0.266 AC: 11019 AN: 41448

American (AMR) AF: 0.192 AC: 2940 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.203 AC: 705 AN: 3472

East Asian (EAS) AF: 0.173 AC: 894 AN: 5170

South Asian (SAS) AF: 0.260 AC: 1254 AN: 4816

European-Finnish (FIN) AF: 0.231 AC: 2446 AN: 10574

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12934 AN: 67976

Other (OTH) AF: 0.217 AC: 458 AN: 2110

Alfa AF: 0.190 Hom.: 4689

Bravo AF: 0.213

Asia WGS AF: 0.217 AC: 754 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	-0.93
CADD	Benign	3.7
DANN	Benign	0.41
PhyloP100		-0.0050
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: rs16898015; hg19: chr8-101174426; COSMIC: COSV52562085; COSMIC: COSV52562085;