rs763608370

Variant names:

• chr20-49905912-C-G
• rs763608370
• NM_006038.4:c.1270G>C

Your query was ambiguous. Multiple possible variants found:

• chr20-49905912-C-G
• chr20-49905912-C-T

Variant summary

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

The NM_006038.4(SPATA2):​c.1270G>C​(p.Ala424Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,459,912 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A424T) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SPATA2 NM_006038.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.28

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=0.0773437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA2	NM_006038.4	c.1270G>C	p.Ala424Pro	missense_variant	Exon 3 of 3	ENST00000289431.10	NP_006029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA2	ENST00000289431.10	c.1270G>C	p.Ala424Pro	missense_variant	Exon 3 of 3	1	NM_006038.4	ENSP00000289431.5
SPATA2	ENST00000422556.1	c.1270G>C	p.Ala424Pro	missense_variant	Exon 3 of 3	2		ENSP00000416799.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459912 Hom.: 0 Cov.: 70 AF XY: 0.00000138 AC XY: 1 AN XY: 726220

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.092
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.035
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.73	.;T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L
PrimateAI	Benign	0.41	T
PROVEAN	Benign	0.080	N;N
REVEL	Benign	0.12
Sift	Benign	0.23	T;T
Sift4G	Benign	0.31	T;T
Polyphen		0.0030	B;B
Vest4		0.075
MutPred		0.12		Loss of helix (P = 0.0076);Loss of helix (P = 0.0076);
MVP		0.16
MPC		0.56
ClinPred		0.40	T
GERP RS		3.8
Varity_R		0.068
gMVP		0.23

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

LitVar

Other links and lift over

dbSNP: rs763608370; hg19: chr20-48522449;