20-49905793-G-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_006038.4(SPATA2):​c.1389C>T​(p.Cys463Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.421 in 1,613,982 control chromosomes in the GnomAD database, including 149,076 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.35 (11207 hom., cov: 33)
  • Exomes 𝑓: 0.43 (137869 hom.)
• Consequence: SPATA2 NM_006038.4 synonymous
• 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=0.5 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

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>T	p.Cys463Cys	synonymous	Exon 3 of 3	NP_006029.1	Q9UM82
	SPATA2	NM_001135773.2		c.1389C>T	p.Cys463Cys	synonymous	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>T	p.Cys463Cys	synonymous	Exon 3 of 3	ENSP00000289431.5	Q9UM82
	SPATA2	ENST00000422556.1	TSL:2	c.1389C>T	p.Cys463Cys	synonymous	Exon 3 of 3	ENSP00000416799.1	Q9UM82
	SPATA2	ENST00000857509.1		c.1389C>T	p.Cys463Cys	synonymous	Exon 3 of 3	ENSP00000527568.1

Frequencies

GnomAD3 genomes AF: 0.353 AC: 53616 AN: 152044 Hom.: 11192 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.442

Gnomad ASJ AF: 0.347

Gnomad EAS AF: 0.344

Gnomad SAS AF: 0.559

Gnomad FIN AF: 0.563

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.361

GnomAD2 exomes AF: 0.436 AC: 109553 AN: 251352 AF XY: 0.443

Gnomad AFR exome AF: 0.121

Gnomad AMR exome AF: 0.506

Gnomad ASJ exome AF: 0.324

Gnomad EAS exome AF: 0.346

Gnomad FIN exome AF: 0.557

Gnomad NFE exome AF: 0.423

Gnomad OTH exome AF: 0.440

GnomAD4 exome AF: 0.428 AC: 625881 AN: 1461820 Hom.: 137869 Cov.: 62 AF XY: 0.433 AC XY: 314747 AN XY: 727206

African (AFR) AF: 0.114 AC: 3833 AN: 33480

American (AMR) AF: 0.495 AC: 22150 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.336 AC: 8788 AN: 26136

East Asian (EAS) AF: 0.342 AC: 13597 AN: 39700

South Asian (SAS) AF: 0.571 AC: 49240 AN: 86254

European-Finnish (FIN) AF: 0.559 AC: 29850 AN: 53406

Middle Eastern (MID) AF: 0.340 AC: 1958 AN: 5766

European-Non Finnish (NFE) AF: 0.424 AC: 472000 AN: 1111960

Other (OTH) AF: 0.405 AC: 24465 AN: 60394

GnomAD4 genome AF: 0.353 AC: 53664 AN: 152162 Hom.: 11207 Cov.: 33 AF XY: 0.367 AC XY: 27276 AN XY: 74392

African (AFR) AF: 0.126 AC: 5227 AN: 41522

American (AMR) AF: 0.443 AC: 6771 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.347 AC: 1205 AN: 3472

East Asian (EAS) AF: 0.344 AC: 1785 AN: 5182

South Asian (SAS) AF: 0.561 AC: 2705 AN: 4824

European-Finnish (FIN) AF: 0.563 AC: 5955 AN: 10584

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.425 AC: 28871 AN: 67978

Other (OTH) AF: 0.362 AC: 763 AN: 2110

Alfa AF: 0.385 Hom.: 38802

Bravo AF: 0.326

Asia WGS AF: 0.459 AC: 1598 AN: 3478

EpiCase AF: 0.395

EpiControl AF: 0.390

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	4.4
DANN	Benign	0.64
PhyloP100		0.50
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=100/0	polymorphism (auto)

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; COSMIC: COSV56865283;