Variant chr17-50547231-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022827.4(SPATA20):c.23T>C(p.Leu8Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000208 in 1,415,064 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00020 ( 1 hom. )

Consequence

SPATA20
NM_022827.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.595

Variant links:

Genes affected

SPATA20 (HGNC:26125): (spermatogenesis associated 20) Predicted to be involved in carbohydrate metabolic process; cell differentiation; and spermatogenesis. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

SPATA20 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.0035066307).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SPATA20	NM_022827.4 linkuse as main transcript	c.23T>C	p.Leu8Ser	missense_variant	1/17	ENST00000006658.11	NP_073738.2
SPATA20	NM_001258372.2 linkuse as main transcript	c.23T>C	p.Leu8Ser	missense_variant	1/16		NP_001245301.1
SPATA20	NM_001258373.2 linkuse as main transcript	c.-213T>C		5_prime_UTR_variant	1/17		NP_001245302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA20	ENST00000006658.11 linkuse as main transcript	c.23T>C	p.Leu8Ser	missense_variant	1/17	1	NM_022827.4	ENSP00000006658		Q8TB22-2

Frequencies

GnomAD3 genomes

AF:

0.000316

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00890

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000357

AC:

AN:

27982

Hom.:

AF XY:

0.000361

AC XY:

AN XY:

16636

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00698

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000561

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000196

AC:

247

AN:

1262864

Hom.:

Cov.:

AF XY:

0.000168

AC XY:

104

AN XY:

618458

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00777

Gnomad4 SAS exome

AF:

0.0000491

Gnomad4 FIN exome

AF:

0.000227

Gnomad4 NFE exome

AF:

0.00000292

Gnomad4 OTH exome

AF:

0.000211

GnomAD4 genome

AF:

0.000315

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000296

AC XY:

AN XY:

74412

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00893

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000431

ExAC

AF:

0.0000770

AC:

Asia WGS

AF:

0.00116

AC:

AN:

3470

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

Oct 12, 2022

The c.23T>C (p.L8S) alteration is located in exon 1 (coding exon 1) of the SPATA20 gene. This alteration results from a T to C substitution at nucleotide position 23, causing the leucine (L) at amino acid position 8 to be replaced by a serine (S). 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

0.16

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.42

CADD

Benign

DANN

Benign

0.69

DEOGEN2

Benign

0.063

.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.056

LIST_S2

Benign

0.54

T;T

MetaRNN

Benign

0.0035

T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.64

PROVEAN

Benign

-0.39

N;N

REVEL

Benign

0.19

Sift

Uncertain

0.012

D;D

Sift4G

Uncertain

0.014

D;D

Polyphen

0.13

B;B

Vest4

0.31

MutPred

0.18

Gain of phosphorylation at L8 (P = 0.0229);Gain of phosphorylation at L8 (P = 0.0229);

MVP

0.13

MPC

0.28

ClinPred

0.034

GERP RS

1.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.12

gMVP

0.70

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