Variant 17-50547242-C-T 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.34C>T(p.Leu12Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000285 in 1,404,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000024 ( 0 hom. )

Consequence

SPATA20
NM_022827.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.819

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=0.065291435).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SPATA20	NM_022827.4 linkuse as main transcript	c.34C>T	p.Leu12Phe	missense_variant	1/17	ENST00000006658.11	NP_073738.2
SPATA20	NM_001258372.2 linkuse as main transcript	c.34C>T	p.Leu12Phe	missense_variant	1/16		NP_001245301.1
SPATA20	NM_001258373.2 linkuse as main transcript	c.-202C>T		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.34C>T	p.Leu12Phe	missense_variant	1/17	1	NM_022827.4	ENSP00000006658		Q8TB22-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152152

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:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000240

AC:

AN:

1252346

Hom.:

Cov.:

AF XY:

0.00000163

AC XY:

AN XY:

612158

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000348

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000387

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000936

Hom.:

Bravo

AF:

0.00000756

Asia WGS

AF:

0.000289

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

Feb 12, 2024

The c.34C>T (p.L12F) alteration is located in exon 1 (coding exon 1) of the SPATA20 gene. This alteration results from a C to T substitution at nucleotide position 34, causing the leucine (L) at amino acid position 12 to be replaced by a phenylalanine (F). 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

0.072

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Benign

0.85

DEOGEN2

Benign

0.053

.;T

Eigen

Benign

-0.99

Eigen_PC

Benign

-1.0

FATHMM_MKL

Benign

0.074

LIST_S2

Benign

0.57

T;T

M_CAP

Benign

0.0065

MetaRNN

Benign

0.065

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Uncertain

0.62

PROVEAN

Benign

-0.11

N;N

REVEL

Benign

0.033

Sift

Benign

0.11

T;T

Sift4G

Pathogenic

0.0

D;D

Polyphen

0.0

B;B

Vest4

0.15

MutPred

0.26

Loss of disorder (P = 0.0788);Loss of disorder (P = 0.0788);

MVP

0.072

MPC

0.64

ClinPred

0.19

GERP RS

1.9

Varity_R

0.070

gMVP

0.43

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