chr17-50977078-T-C

Position:

• chr17-50977078-T-C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0200

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPAG9	NM_001130528.3	c.3523+30A>G		intron_variant		ENST00000262013.12	NP_001124000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPAG9	ENST00000262013.12	c.3523+30A>G		intron_variant		1	NM_001130528.3	ENSP00000262013.7

Frequencies

GnomAD3 genomes AF: 0.420 AC: 63759 AN: 151908 Hom.: 13773 Cov.: 32

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

GnomAD3 exomes AF: 0.425 AC: 104420 AN: 245560 Hom.: 22998 AF XY: 0.423 AC XY: 56305 AN XY: 133080

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 SAS exome AF: 0.355

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.: 15 AF XY: 0.446 AC XY: 263454 AN XY: 590560

Gnomad4 AFR exome AF: 0.351

Gnomad4 AMR exome AF: 0.474

Gnomad4 ASJ exome AF: 0.460

Gnomad4 EAS exome AF: 0.199

Gnomad4 SAS exome AF: 0.361

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.473

Gnomad4 OTH exome AF: 0.434

GnomAD4 genome AF: 0.420 AC: 63806 AN: 152026 Hom.: 13784 Cov.: 32 AF XY: 0.415 AC XY: 30799 AN XY: 74290

Gnomad4 AFR AF: 0.354

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.460

Gnomad4 EAS AF: 0.210

Gnomad4 SAS AF: 0.338

Gnomad4 FIN AF: 0.389

Gnomad4 NFE AF: 0.473

Gnomad4 OTH AF: 0.436

Alfa AF: 0.448 Hom.: 2950

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
DANN	Benign	0.74

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: rs9332407; hg19: chr17-49054439; COSMIC: COSV56233080; COSMIC: COSV56233080;