Genetic Variant NM_001130528.3:c.3523+30A>G (chr17-50977078-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001130528.3(SPAG9):c.3523+30A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.445 in 1,308,896 control chromosomes in the GnomAD database, including 132,835 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 0.42 ( 13784 hom., cov: 32)

Exomes 𝑓: 0.45 ( 119051 hom. )

Consequence

SPAG9
NM_001130528.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0200

Publications

13 publications found

Variant links:

Genes affected

SPAG9 (HGNC:14524): (sperm associated antigen 9) This gene encodes a member of the cancer testis antigen gene family. The encoded protein functions as a scaffold protein that structurally organizes mitogen-activated protein kinases and mediates c-Jun-terminal kinase signaling. This protein also binds to kinesin-1 and may be involved in microtubule-based membrane transport. This protein may play a role in tumor growth and development. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2011]

SPAG9 Gene-Disease associations (from GenCC):

schizophrenia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

SPAG9 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

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

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.469 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPAG9	NM_001130528.3 link	c.3523+30A>G		intron_variant	Intron 27 of 29	ENST00000262013.12	NP_001124000.1	O60271-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPAG9	ENST00000262013.12 link	c.3523+30A>G		intron_variant	Intron 27 of 29	1	NM_001130528.3	ENSP00000262013.7		O60271-1

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

63759

AN:

151908

Hom.:

13773

Cov.:

show subpopulations

Gnomad AFR

AF:

0.354

Gnomad AMI

AF:

0.591

Gnomad AMR

AF:

0.457

Gnomad ASJ

AF:

0.460

Gnomad EAS

AF:

0.211

Gnomad SAS

AF:

0.338

Gnomad FIN

AF:

0.389

Gnomad MID

AF:

0.402

Gnomad NFE

AF:

0.473

Gnomad OTH

AF:

0.434

GnomAD2 exomes

AF:

0.425

AC:

104420

AN:

245560

AF XY:

0.423

show subpopulations

Gnomad AFR exome

AF:

0.358

Gnomad AMR exome

AF:

0.481

Gnomad ASJ exome

AF:

0.461

Gnomad EAS exome

AF:

0.215

Gnomad FIN exome

AF:

0.396

Gnomad NFE exome

AF:

0.473

Gnomad OTH exome

AF:

0.437

GnomAD4 exome

AF:

0.448

AC:

518697

AN:

1156870

Hom.:

119051

Cov.:

AF XY:

0.446

AC XY:

263454

AN XY:

590560

show subpopulations

African (AFR)

AF:

0.351

AC:

9493

AN:

27054

American (AMR)

AF:

0.474

AC:

20083

AN:

42368

Ashkenazi Jewish (ASJ)

AF:

0.460

AC:

11039

AN:

23996

East Asian (EAS)

AF:

0.199

AC:

7579

AN:

38166

South Asian (SAS)

AF:

0.361

AC:

28639

AN:

79432

European-Finnish (FIN)

AF:

0.401

AC:

21106

AN:

52572

Middle Eastern (MID)

AF:

0.433

AC:

2247

AN:

5184

European-Non Finnish (NFE)

AF:

0.473

AC:

396809

AN:

838070

Other (OTH)

AF:

0.434

AC:

21702

AN:

50028

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

13937

27874

41811

55748

69685

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10188

20376

30564

40752

50940

<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:

0.420

AC:

63806

AN:

152026

Hom.:

13784

Cov.:

AF XY:

0.415

AC XY:

30799

AN XY:

74290

show subpopulations

African (AFR)

AF:

0.354

AC:

14674

AN:

41456

American (AMR)

AF:

0.457

AC:

6972

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.460

AC:

1595

AN:

3466

East Asian (EAS)

AF:

0.210

AC:

1091

AN:

5184

South Asian (SAS)

AF:

0.338

AC:

1632

AN:

4822

European-Finnish (FIN)

AF:

0.389

AC:

4111

AN:

10560

Middle Eastern (MID)

AF:

0.405

AC:

119

AN:

294

European-Non Finnish (NFE)

AF:

0.473

AC:

32155

AN:

67952

Other (OTH)

AF:

0.436

AC:

919

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1880

3759

5639

7518

9398

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

592

1184

1776

2368

2960

<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:

0.446

Hom.:

3005

Bravo

AF:

0.422

Asia WGS

AF:

0.281

AC:

976

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

3.9

(source)

DANN

Benign

0.74

PhyloP100

0.020

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