dbSNP rs495337: SPATA2:p.Cys463Cys (chr20-49905793-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.500

Variant links:

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]

SPATA2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA2	NM_006038.4 link	c.1389C>T	p.Cys463Cys	synonymous_variant	Exon 3 of 3	ENST00000289431.10	NP_006029.1	Q9UM82B4DID4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA2	ENST00000289431.10 link	c.1389C>T	p.Cys463Cys	synonymous_variant	Exon 3 of 3	1	NM_006038.4	ENSP00000289431.5		Q9UM82
SPATA2	ENST00000422556.1 link	c.1389C>T	p.Cys463Cys	synonymous_variant	Exon 3 of 3	2		ENSP00000416799.1		Q9UM82

Frequencies

GnomAD3 genomes

AF:

0.353

AC:

53616

AN:

152044

Hom.:

11192

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.436

AC:

109553

AN:

251352

Hom.:

25314

AF XY:

0.443

AC XY:

60246

AN XY:

135856

show subpopulations

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 SAS exome

AF:

0.575

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.:

AF XY:

0.433

AC XY:

314747

AN XY:

727206

show subpopulations

Gnomad4 AFR exome

AF:

0.114

Gnomad4 AMR exome

AF:

0.495

Gnomad4 ASJ exome

AF:

0.336

Gnomad4 EAS exome

AF:

0.342

Gnomad4 SAS exome

AF:

0.571

Gnomad4 FIN exome

AF:

0.559

Gnomad4 NFE exome

AF:

0.424

Gnomad4 OTH exome

AF:

0.405

GnomAD4 genome

AF:

0.353

AC:

53664

AN:

152162

Hom.:

11207

Cov.:

AF XY:

0.367

AC XY:

27276

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.126

Gnomad4 AMR

AF:

0.443

Gnomad4 ASJ

AF:

0.347

Gnomad4 EAS

AF:

0.344

Gnomad4 SAS

AF:

0.561

Gnomad4 FIN

AF:

0.563

Gnomad4 NFE

AF:

0.425

Gnomad4 OTH

AF:

0.362

Alfa

AF:

0.396

Hom.:

18113

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.65

CADD

Benign

4.4

DANN

Benign

0.64

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over