NM_006038.4:c.1389C>G

Variant names:

• chr20-49905793-G-C
• rs495337
• NM_006038.4:c.1389C>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_006038.4(SPATA2):​c.1389C>G​(p.Cys463Trp) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPATA2 NM_006038.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.500
• Publications: 66 publications found

Genes affected

SPATA2 (HGNC:14681): (spermatogenesis associated 2) Enables signaling receptor complex adaptor activity and ubiquitin-specific protease binding activity. Involved in several processes, including protein deubiquitination; regulation of necroptotic process; and regulation of tumor necrosis factor-mediated signaling pathway. Located in cytoplasm; fibrillar center; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.912

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006038.4. 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
	SPATA2	NM_006038.4	MANE Select	c.1389C>G	p.Cys463Trp	missense	Exon 3 of 3	NP_006029.1	Q9UM82
	SPATA2	NM_001135773.2		c.1389C>G	p.Cys463Trp	missense	Exon 3 of 3	NP_001129245.1	Q9UM82

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA2	ENST00000289431.10	TSL:1 MANE Select	c.1389C>G	p.Cys463Trp	missense	Exon 3 of 3	ENSP00000289431.5	Q9UM82
	SPATA2	ENST00000422556.1	TSL:2	c.1389C>G	p.Cys463Trp	missense	Exon 3 of 3	ENSP00000416799.1	Q9UM82
	SPATA2	ENST00000857509.1		c.1389C>G	p.Cys463Trp	missense	Exon 3 of 3	ENSP00000527568.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 38802

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.99
BayesDel_addAF	Pathogenic	0.23	D
BayesDel_noAF	Uncertain	0.090
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	0.13
Eigen_PC	Benign	-0.011
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.89	D
M_CAP	Pathogenic	0.45	D
MetaRNN	Pathogenic	0.91	D
MetaSVM	Uncertain	-0.057	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		0.50
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-4.1	D
REVEL	Uncertain	0.60
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.85
MutPred		0.63		Loss of disorder (P = 0.059)
MVP		0.14
MPC		0.94
ClinPred		0.99	D
GERP RS		-3.2
Varity_R		0.85
gMVP		0.62
Mutation Taster		=32/68	disease causing

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: rs495337; hg19: chr20-48522330;