Variant chr20-49906071-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_006038.4(SPATA2):c.1111C>T(p.Arg371Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00000412 in 1,455,818 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

SPATA2
NM_006038.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.44

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.32914293).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA2	NM_006038.4 linkuse as main transcript	c.1111C>T	p.Arg371Cys	missense_variant	3/3	ENST00000289431.10	NP_006029.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA2	ENST00000289431.10 linkuse as main transcript	c.1111C>T	p.Arg371Cys	missense_variant	3/3	1	NM_006038.4	ENSP00000289431	P1
SPATA2	ENST00000422556.1 linkuse as main transcript	c.1111C>T	p.Arg371Cys	missense_variant	3/3	2		ENSP00000416799	P1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000812

AC:

AN:

246426

Hom.:

AF XY:

0.00000749

AC XY:

AN XY:

133470

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000545

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000412

AC:

AN:

1455818

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724256

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 28, 2023

The c.1111C>T (p.R371C) alteration is located in exon 3 (coding exon 2) of the SPATA2 gene. This alteration results from a C to T substitution at nucleotide position 1111, causing the arginine (R) at amino acid position 371 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.20

BayesDel_addAF

Uncertain

0.11

BayesDel_noAF

Uncertain

-0.080

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.023

T;T

Eigen

Uncertain

0.65

Eigen_PC

Uncertain

0.61

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.87

.;D

M_CAP

Uncertain

0.10

MetaRNN

Benign

0.33

T;T

MetaSVM

Benign

-0.43

MutationAssessor

Uncertain

2.1

M;M

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.54

PROVEAN

Benign

-0.52

N;N

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0010

D;D

Polyphen

1.0

D;D

Vest4

0.47

MutPred

0.39

Loss of solvent accessibility (P = 3e-04);Loss of solvent accessibility (P = 3e-04);

MVP

0.23

MPC

0.77

ClinPred

0.84

GERP RS

4.3

Varity_R

0.24

gMVP

0.26

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over