20-49905793-G-T

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_006038.4(SPATA2):​c.1389C>A​(p.Cys463*) variant causes a stop gained 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 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.500
• Publications: 0 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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>A	p.Cys463*	stop_gained	Exon 3 of 3	NP_006029.1	Q9UM82
	SPATA2	NM_001135773.2		c.1389C>A	p.Cys463*	stop_gained	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>A	p.Cys463*	stop_gained	Exon 3 of 3	ENSP00000289431.5	Q9UM82
	SPATA2	ENST00000422556.1	TSL:2	c.1389C>A	p.Cys463*	stop_gained	Exon 3 of 3	ENSP00000416799.1	Q9UM82
	SPATA2	ENST00000857509.1		c.1389C>A	p.Cys463*	stop_gained	Exon 3 of 3	ENSP00000527568.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 62

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.49	D
BayesDel_noAF	Pathogenic	0.47
CADD	Pathogenic	36
DANN	Uncertain	0.99
Eigen	Uncertain	0.27
Eigen_PC	Benign	0.034
FATHMM_MKL	Uncertain	0.91	D
PhyloP100		0.50
Vest4		0.25
GERP RS		-3.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=19/181	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;