Variant chr1-16409629-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198546.1(SPATA21):c.559G>A(p.Glu187Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000192 in 1,612,574 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 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000020 ( 0 hom. )

Consequence

SPATA21
NM_198546.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.281

Variant links:

Genes affected

SPATA21 (HGNC:28026): (spermatogenesis associated 21) Predicted to enable calcium ion binding activity. [provided by Alliance of Genome Resources, Apr 2022]

SPATA21 links:

SPATA21 (HGNC:):

SPATA21 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11107284).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA21	NM_198546.1 linkuse as main transcript	c.559G>A	p.Glu187Lys	missense_variant	6/13	ENST00000335496.5	NP_940948.1	Q7Z572-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SPATA21	ENST00000335496.5 linkuse as main transcript	c.559G>A	p.Glu187Lys	missense_variant	6/13	1	NM_198546.1	ENSP00000335612.1	Q7Z572-1
SPATA21	ENST00000540400.1 linkuse as main transcript	c.490G>A	p.Glu164Lys	missense_variant	4/11	1		ENSP00000440046.1	Q7Z572-2
SPATA21	ENST00000466212.5 linkuse as main transcript	n.1643G>A		non_coding_transcript_exon_variant	7/17	2

Frequencies

GnomAD3 genomes

AF:

0.0000131

AC:

AN:

152206

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:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000121

AC:

AN:

248730

Hom.:

AF XY:

0.0000223

AC XY:

AN XY:

134726

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:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000178

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000199

AC:

AN:

1460368

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

726508

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:

0.0000464

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000189

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.0000131

AC:

AN:

152206

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74358

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:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000330

AC:

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

Jan 16, 2024

The c.559G>A (p.E187K) alteration is located in exon 6 (coding exon 4) of the SPATA21 gene. This alteration results from a G to A substitution at nucleotide position 559, causing the glutamic acid (E) at amino acid position 187 to be replaced by a lysine (K). 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

0.086

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0036

T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.82

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.69

T;T

M_CAP

Benign

0.047

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.0

M;.

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.098

Sift

Uncertain

0.0070

D;D

Sift4G

Uncertain

0.044

D;T

Polyphen

0.81

P;.

Vest4

0.18

MutPred

0.36

Gain of MoRF binding (P = 0.0068);.;

MVP

0.22

MPC

0.11

ClinPred

0.26

GERP RS

-0.65

Varity_R

0.074

gMVP

0.33

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