17-50970845-T-C

Position:

• chr17-50970845-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2 PP2 BP4_Moderate

The NM_001130528.3(SPAG9):​c.3712A>G​(p.Ser1238Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 31)
• Consequence: SPAG9 NM_001130528.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.38

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP2: Missense variant in gene, where missense usually causes diseases (based on misZ statistic), SPAG9. . Gene score misZ 3.1339 (greater than the threshold 3.09). Trascript score misZ 3.8344 (greater than threshold 3.09). GenCC has associacion of gene with schizophrenia.
• BP4: Computational evidence support a benign effect (MetaRNN=0.069619715).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPAG9	NM_001130528.3	c.3712A>G	p.Ser1238Gly	missense_variant	29/30	ENST00000262013.12	NP_001124000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPAG9	ENST00000262013.12	c.3712A>G	p.Ser1238Gly	missense_variant	29/30	1	NM_001130528.3	ENSP00000262013.7

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 31

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 07, 2024

The c.3712A>G (p.S1238G) alteration is located in exon 29 (coding exon 29) of the SPAG9 gene. This alteration results from a A to G substitution at nucleotide position 3712, causing the serine (S) at amino acid position 1238 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.067
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.16	T;T;.;.;.
Eigen	Benign	-0.11
Eigen_PC	Benign	0.042
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.89	D;D;D;D;D
M_CAP	Benign	0.0032	T
MetaRNN	Benign	0.070	T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.63	N;.;.;.;.
PrimateAI	Benign	0.41	T
PROVEAN	Benign	-0.34	N;.;N;N;N
REVEL	Benign	0.039
Sift	Benign	0.34	T;.;T;T;T
Sift4G	Benign	0.42	T;T;T;T;T
Polyphen		0.0010	B;.;.;B;B
Vest4		0.14
MutPred		0.25		Loss of glycosylation at S1238 (P = 0.0607);.;.;.;.;
MVP		0.24
MPC		0.35
ClinPred		0.12	T
GERP RS		4.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.091
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-49048206;