Variant 17-50548406-C-G 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.249C>G(p.His83Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,748 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SPATA20
NM_022827.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.180

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=0.060806155).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SPATA20	NM_022827.4 linkuse as main transcript	c.249C>G	p.His83Gln	missense_variant	3/17	ENST00000006658.11	NP_073738.2
SPATA20	NM_001258372.2 linkuse as main transcript	c.201C>G	p.His67Gln	missense_variant	2/16		NP_001245301.1
SPATA20	NM_001258373.2 linkuse as main transcript	c.69C>G	p.His23Gln	missense_variant	3/17		NP_001245302.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA20	ENST00000006658.11 linkuse as main transcript	c.249C>G	p.His83Gln	missense_variant	3/17	1	NM_022827.4	ENSP00000006658		Q8TB22-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461748

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Dec 28, 2022

The c.249C>G (p.H83Q) alteration is located in exon 3 (coding exon 3) of the SPATA20 gene. This alteration results from a C to G substitution at nucleotide position 249, causing the histidine (H) at amino acid position 83 to be replaced by a glutamine (Q). 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

0.12

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.78

DEOGEN2

Benign

0.027

.;.;T;T

Eigen

Benign

-0.96

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.35

LIST_S2

Uncertain

0.96

D;D;D;D

M_CAP

Benign

0.0059

MetaRNN

Benign

0.061

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.26

.;.;N;.

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.24

PROVEAN

Benign

0.55

.;N;N;.

REVEL

Benign

0.013

Sift

Benign

0.65

.;T;T;.

Sift4G

Benign

0.63

T;T;T;T

Polyphen

0.0040, 0.0

.;B;B;.

Vest4

0.19

MutPred

0.38

.;.;Gain of ubiquitination at K69 (P = 0.0882);Gain of ubiquitination at K69 (P = 0.0882);

MVP

0.20

MPC

0.20

ClinPred

0.043

GERP RS

1.1

Varity_R

0.043

gMVP

0.21

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over