rs2073869

Positions:

• chr9-132888429-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001316900.2(SPACA9):​c.483+4C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,613,394 control chromosomes in the GnomAD database, including 26,454 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.19 (2791 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23663 hom.)
• Consequence: SPACA9 NM_001316900.2 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.126

Genes affected

SPACA9 (HGNC:1367): (sperm acrosome associated 9) Predicted to enable calcium-dependent protein binding activity. Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

SPACA9 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPACA9	NM_001316897.2	c.487C>T	p.Leu163Leu	synonymous_variant	4/4	ENST00000356311.10	NP_001303826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPACA9	ENST00000356311.10	c.487C>T	p.Leu163Leu	synonymous_variant	4/4	2	NM_001316897.2	ENSP00000348659.5
SPACA9	ENST00000372136.7	c.487C>T	p.Leu163Leu	synonymous_variant	4/4	1		ENSP00000361209.3
SPACA9	ENST00000350499.6	c.487C>T	p.Leu163Leu	synonymous_variant	4/5	1		ENSP00000298546.7

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28533 AN: 151938 Hom.: 2789 Cov.: 32

Gnomad AFR AF: 0.198

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.118

Gnomad EAS AF: 0.253

Gnomad SAS AF: 0.186

Gnomad FIN AF: 0.280

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.181

Gnomad OTH AF: 0.174

GnomAD3 exomes AF: 0.185 AC: 46066 AN: 249156 Hom.: 4541 AF XY: 0.184 AC XY: 24813 AN XY: 134896

Gnomad AFR exome AF: 0.202

Gnomad AMR exome AF: 0.146

Gnomad ASJ exome AF: 0.118

Gnomad EAS exome AF: 0.267

Gnomad SAS exome AF: 0.173

Gnomad FIN exome AF: 0.273

Gnomad NFE exome AF: 0.173

Gnomad OTH exome AF: 0.184

GnomAD4 exome AF: 0.177 AC: 258023 AN: 1461334 Hom.: 23663 Cov.: 35 AF XY: 0.178 AC XY: 129063 AN XY: 726946

Gnomad4 AFR exome AF: 0.202

Gnomad4 AMR exome AF: 0.144

Gnomad4 ASJ exome AF: 0.116

Gnomad4 EAS exome AF: 0.252

Gnomad4 SAS exome AF: 0.176

Gnomad4 FIN exome AF: 0.274

Gnomad4 NFE exome AF: 0.172

Gnomad4 OTH exome AF: 0.176

GnomAD4 genome AF: 0.188 AC: 28543 AN: 152060 Hom.: 2791 Cov.: 32 AF XY: 0.190 AC XY: 14095 AN XY: 74320

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.118

Gnomad4 EAS AF: 0.253

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.280

Gnomad4 NFE AF: 0.181

Gnomad4 OTH AF: 0.173

Alfa AF: 0.176 Hom.: 3112

Bravo AF: 0.178

Asia WGS AF: 0.211 AC: 735 AN: 3478

EpiCase AF: 0.168

EpiControl AF: 0.167

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs2073869; hg19: chr9-135763816; COSMIC: COSV53763810; COSMIC: COSV53763810;