20-49905711-G-C

Variant names:

• chr20-49905711-G-C
• NM_006038.4:c.1471C>G

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_006038.4(SPATA2):​c.1471C>G​(p.Pro491Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA2 NM_006038.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.56
• 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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.35750136).

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.1471C>G	p.Pro491Ala	missense	Exon 3 of 3	NP_006029.1	Q9UM82
	SPATA2	NM_001135773.2		c.1471C>G	p.Pro491Ala	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.1471C>G	p.Pro491Ala	missense	Exon 3 of 3	ENSP00000289431.5	Q9UM82
	SPATA2	ENST00000422556.1	TSL:2	c.1471C>G	p.Pro491Ala	missense	Exon 3 of 3	ENSP00000416799.1	Q9UM82
	SPATA2	ENST00000857509.1		c.1471C>G	p.Pro491Ala	missense	Exon 3 of 3	ENSP00000527568.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Uncertain	0.020	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.026	T
Eigen	Uncertain	0.24
Eigen_PC	Uncertain	0.28
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.36	T
MetaSVM	Benign	-0.77	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		2.6
PrimateAI	Benign	0.46	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.21
Sift	Benign	0.066	T
Sift4G	Benign	0.14	T
Polyphen		0.79	P
Vest4		0.45
MutPred		0.71		Loss of loop (P = 0.0288)
MVP		0.27
MPC		0.79
ClinPred		0.57	D
GERP RS		5.1
Varity_R		0.055
gMVP		0.12
Mutation Taster		=95/5	polymorphism

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

hg19: chr20-48522248;