Variant chr17-50548816-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_022827.4(SPATA20):c.368A>G(p.Tyr123Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00013 in 1,611,952 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SPATA20
NM_022827.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.16

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 Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.892

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SPATA20	NM_022827.4 linkuse as main transcript	c.368A>G	p.Tyr123Cys	missense_variant	5/17	ENST00000006658.11	NP_073738.2
SPATA20	NM_001258372.2 linkuse as main transcript	c.320A>G	p.Tyr107Cys	missense_variant	4/16		NP_001245301.1
SPATA20	NM_001258373.2 linkuse as main transcript	c.188A>G	p.Tyr63Cys	missense_variant	5/17		NP_001245302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA20	ENST00000006658.11 linkuse as main transcript	c.368A>G	p.Tyr123Cys	missense_variant	5/17	1	NM_022827.4	ENSP00000006658		Q8TB22-2

Frequencies

GnomAD3 genomes

AF:

0.0000592

AC:

AN:

151930

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000189

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000194

AC:

AN:

247586

Hom.:

AF XY:

0.000156

AC XY:

AN XY:

134212

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000425

Gnomad NFE exome

AF:

0.000341

Gnomad OTH exome

AF:

0.000166

GnomAD4 exome

AF:

0.000137

AC:

200

AN:

1460022

Hom.:

Cov.:

AF XY:

0.000127

AC XY:

AN XY:

726258

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000603

Gnomad4 NFE exome

AF:

0.000142

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.0000592

AC:

AN:

151930

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74220

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000189

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000177

Hom.:

Bravo

AF:

0.0000416

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000231

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000237

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

Jun 21, 2022

The c.368A>G (p.Y123C) alteration is located in exon 5 (coding exon 5) of the SPATA20 gene. This alteration results from a A to G substitution at nucleotide position 368, causing the tyrosine (Y) at amino acid position 123 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

Pathogenic

0.94

BayesDel_addAF

Pathogenic

0.32

BayesDel_noAF

Pathogenic

0.22

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

.;.;T;T

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.94

D;D;D;D

M_CAP

Uncertain

0.17

MetaRNN

Pathogenic

0.89

D;D;D;D

MetaSVM

Uncertain

0.078

MutationAssessor

Pathogenic

3.6

.;.;H;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Pathogenic

0.79

PROVEAN

Pathogenic

-8.3

.;D;D;.

REVEL

Pathogenic

0.73

Sift

Pathogenic

0.0

.;D;D;.

Sift4G

Pathogenic

0.0

D;D;D;D

Polyphen

1.0

.;D;D;.

Vest4

0.82

MVP

0.80

MPC

0.73

ClinPred

0.99

GERP RS

4.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.95

gMVP

0.83

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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