chr20-49905951-T-G

Position:

• chr20-49905951-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_006038.4(SPATA2):​c.1231A>C​(p.Ser411Arg) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPATA2 NM_006038.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.689

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.084498525).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA2	NM_006038.4	c.1231A>C	p.Ser411Arg	missense_variant	3/3	ENST00000289431.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA2	ENST00000289431.10	c.1231A>C	p.Ser411Arg	missense_variant	3/3	1	NM_006038.4	P1
SPATA2	ENST00000422556.1	c.1231A>C	p.Ser411Arg	missense_variant	3/3	2		P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 69

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.41
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	7.6
DANN	Uncertain	0.99
DEOGEN2	Benign	0.022	T;T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Uncertain	0.86	D
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.084	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.1	M;M
MutationTaster	Benign	0.88	N;N;N
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-1.0	N;N
REVEL	Benign	0.12
Sift	Benign	0.072	T;T
Sift4G	Uncertain	0.040	D;D
Polyphen		0.0020	B;B
Vest4		0.14
MutPred		0.18		Loss of glycosylation at S411 (P = 0.0048);Loss of glycosylation at S411 (P = 0.0048);
MVP		0.16
MPC		0.61
ClinPred		0.22	T
GERP RS		-7.1
Varity_R		0.073
gMVP		0.37

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: chr20-48522488;