Variant 17-50549072-G-T 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.546G>T(p.Met182Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000545 in 1,613,500 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000049 ( 0 hom. )

Consequence

SPATA20
NM_022827.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.32

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:

SPATA20 (HGNC:):

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, 0.843

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA20	NM_022827.4 linkuse as main transcript	c.546G>T	p.Met182Ile	missense_variant	6/17	ENST00000006658.11	NP_073738.2	Q8TB22-2
SPATA20	NM_001258372.2 linkuse as main transcript	c.498G>T	p.Met166Ile	missense_variant	5/16		NP_001245301.1	Q8TB22-1
SPATA20	NM_001258373.2 linkuse as main transcript	c.366G>T	p.Met122Ile	missense_variant	6/17		NP_001245302.1	Q8TB22-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA20	ENST00000006658.11 linkuse as main transcript	c.546G>T	p.Met182Ile	missense_variant	6/17	1	NM_022827.4	ENSP00000006658.6		Q8TB22-2

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

152178

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000479

AC:

AN:

250392

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135636

show subpopulations

Gnomad AFR exome

AF:

0.000309

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000354

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000493

AC:

AN:

1461322

Hom.:

Cov.:

AF XY:

0.0000371

AC XY:

AN XY:

726996

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000549

Gnomad4 OTH exome

AF:

0.0000497

GnomAD4 genome

AF:

0.000105

AC:

AN:

152178

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000226

Hom.:

Bravo

AF:

0.000136

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000494

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 30, 2024

The c.546G>T (p.M182I) alteration is located in exon 6 (coding exon 6) of the SPATA20 gene. This alteration results from a G to T substitution at nucleotide position 546, causing the methionine (M) at amino acid position 182 to be replaced by an isoleucine (I). 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

0.95

BayesDel_addAF

Uncertain

0.080

BayesDel_noAF

Pathogenic

0.18

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.33

.;.;T;T

Eigen

Pathogenic

0.95

Eigen_PC

Pathogenic

0.87

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Pathogenic

1.0

D;D;D;D

M_CAP

Benign

0.047

MetaRNN

Pathogenic

0.84

D;D;D;D

MetaSVM

Uncertain

-0.10

MutationAssessor

Pathogenic

3.5

.;.;H;.

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.5

.;D;D;.

REVEL

Uncertain

0.58

Sift

Uncertain

0.0070

.;D;D;.

Sift4G

Uncertain

0.014

D;D;D;D

Polyphen

0.99, 1.0

.;D;D;.

Vest4

0.90

MutPred

0.73

.;.;Loss of glycosylation at P165 (P = 0.1182);Loss of glycosylation at P165 (P = 0.1182);

MVP

0.47

MPC

0.81

ClinPred

0.92

GERP RS

4.9

Varity_R

0.81

gMVP

0.85

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.39

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.39

Position offset: 28

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