Genetic Variant SPACA9:p.Leu163Leu (chr9-132888429-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_001316897.2(SPACA9):c.487C>T(p.Leu163Leu) variant causes a synonymous 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. 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_001316897.2 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.126

Publications

24 publications found

Variant links:

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 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP7

Synonymous conserved (PhyloP=0.126 with no splicing effect.

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 rank	MANE	Protein	UniProt
SPACA9	NM_001316897.2 link	c.487C>T	p.Leu163Leu	synonymous_variant	Exon 4 of 4	ENST00000356311.10	NP_001303826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
SPACA9	ENST00000356311.10 link	c.487C>T	p.Leu163Leu	synonymous_variant	Exon 4 of 4	2	NM_001316897.2	ENSP00000348659.5
SPACA9	ENST00000372136.7 link	c.487C>T	p.Leu163Leu	synonymous_variant	Exon 4 of 4	1		ENSP00000361209.3
SPACA9	ENST00000350499.6 link	c.487C>T	p.Leu163Leu	synonymous_variant	Exon 4 of 5	1		ENSP00000298546.7

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28533

AN:

151938

Hom.:

2789

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.178

AC XY:

129063

AN XY:

726946

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

13496

26992

40489

53985

67481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6660

13320

19980

26640

33300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.188

AC:

28543

AN:

152060

Hom.:

2791

Cov.:

AF XY:

0.190

AC XY:

14095

AN XY:

74320

show subpopulations

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:

AN:

294

European-Non Finnish (NFE)

AF:

0.181

AC:

12268

AN:

67952

Other (OTH)

AF:

0.173

AC:

367

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

1128

2255

3383

4510

5638

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

320

640

960

1280

1600

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.1

(source)

DANN

Benign

0.80

PhyloP100

0.13

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over