9-132888429-C-T

Variant names:

• chr9-132888429-C-T
• rs2073869
• NM_001316897.2:c.487C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 24 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001316900.2. 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
	SPACA9	NM_001316897.2	MANE Select	c.487C>T	p.Leu163Leu	synonymous	Exon 4 of 4	NP_001303826.1	Q96E40-1
	SPACA9	NM_001316898.2		c.487C>T	p.Leu163Leu	synonymous	Exon 4 of 4	NP_001303827.1	Q96E40-1
	SPACA9	NM_018956.5		c.487C>T	p.Leu163Leu	synonymous	Exon 4 of 5	NP_061829.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPACA9	ENST00000356311.10	TSL:2 MANE Select	c.487C>T	p.Leu163Leu	synonymous	Exon 4 of 4	ENSP00000348659.5	Q96E40-1
	SPACA9	ENST00000372136.7	TSL:1	c.487C>T	p.Leu163Leu	synonymous	Exon 4 of 4	ENSP00000361209.3	Q96E40-1
	SPACA9	ENST00000350499.6	TSL:1	c.487C>T	p.Leu163Leu	synonymous	Exon 4 of 5	ENSP00000298546.7	Q96E40-2

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

GnomAD2 exomes AF: 0.185 AC: 46066 AN: 249156 AF XY: 0.184

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 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

African (AFR) AF: 0.202 AC: 6760 AN: 33470

American (AMR) AF: 0.144 AC: 6443 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.116 AC: 3023 AN: 26132

East Asian (EAS) AF: 0.252 AC: 10000 AN: 39682

South Asian (SAS) AF: 0.176 AC: 15141 AN: 86234

European-Finnish (FIN) AF: 0.274 AC: 14560 AN: 53128

Middle Eastern (MID) AF: 0.139 AC: 803 AN: 5768

European-Non Finnish (NFE) AF: 0.172 AC: 190688 AN: 1111836

Other (OTH) AF: 0.176 AC: 10605 AN: 60384

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

African (AFR) AF: 0.197 AC: 8187 AN: 41474

American (AMR) AF: 0.130 AC: 1990 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.118 AC: 408 AN: 3470

East Asian (EAS) AF: 0.253 AC: 1306 AN: 5160

South Asian (SAS) AF: 0.187 AC: 896 AN: 4804

European-Finnish (FIN) AF: 0.280 AC: 2967 AN: 10592

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.181 AC: 12268 AN: 67952

Other (OTH) AF: 0.173 AC: 367 AN: 2116

Alfa AF: 0.177 Hom.: 3797

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.1
DANN	Benign	0.80
PhyloP100		0.13
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: rs2073869; hg19: chr9-135763816; COSMIC: COSV53763810; COSMIC: COSV53763810;