dbSNP rs183875038: SPATA2:p.Pro309Leu (chr20-49906256-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_006038.4(SPATA2):c.926C>T(p.Pro309Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000147 in 1,569,402 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

SPATA2
NM_006038.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 6.01

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 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=0.06982803).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA2	NM_006038.4 link	c.926C>T	p.Pro309Leu	missense_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.926C>T	p.Pro309Leu	missense_variant	Exon 3 of 3	1	NM_006038.4	ENSP00000289431.5		Q9UM82
SPATA2	ENST00000422556.1 link	c.926C>T	p.Pro309Leu	missense_variant	Exon 3 of 3	2		ENSP00000416799.1		Q9UM82

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152168

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000280

AC:

AN:

214308

Hom.:

AF XY:

0.0000351

AC XY:

AN XY:

113926

show subpopulations

Gnomad AFR exome

AF:

0.0000646

Gnomad AMR exome

AF:

0.0000321

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000138

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000102

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000134

AC:

AN:

1417116

Hom.:

Cov.:

AF XY:

0.0000143

AC XY:

AN XY:

699114

show subpopulations

Gnomad4 AFR exome

AF:

0.0000612

Gnomad4 AMR exome

AF:

0.0000243

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000368

Gnomad4 OTH exome

AF:

0.0000343

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152286

Hom.:

Cov.:

AF XY:

0.0000537

AC XY:

AN XY:

74466

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000756

ExAC

AF:

0.0000413

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.34

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.030

T;T

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.066

FATHMM_MKL

Uncertain

0.94

LIST_S2

Benign

0.72

.;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.070

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.7

L;L

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.090

Sift

Uncertain

0.0020

D;D

Sift4G

Benign

0.092

T;T

Polyphen

0.34

B;B

Vest4

0.029

MVP

0.12

MPC

0.22

ClinPred

0.12

GERP RS

4.7

Varity_R

0.061

gMVP

0.27

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