Variant 1-16403824-T-C 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.904A>G(p.Met302Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,458,538 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: not found (cov: 30)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

SPATA21
NM_198546.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.700

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:

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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=0.08842531).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA21	NM_198546.1 linkuse as main transcript	c.904A>G	p.Met302Val	missense_variant	10/13	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.904A>G	p.Met302Val	missense_variant	10/13	1	NM_198546.1	ENSP00000335612.1	Q7Z572-1
SPATA21	ENST00000540400.1 linkuse as main transcript	c.835A>G	p.Met279Val	missense_variant	8/11	1		ENSP00000440046.1	Q7Z572-2
SPATA21	ENST00000491418.5 linkuse as main transcript	c.28A>G	p.Met10Val	missense_variant	2/5	5		ENSP00000420753.1	H7C5T0
SPATA21	ENST00000466212.5 linkuse as main transcript	n.2196A>G		non_coding_transcript_exon_variant	12/17	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000404

AC:

AN:

247476

Hom.:

AF XY:

0.00

AC XY:

AN XY:

133512

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:

0.0000334

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1458538

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

725270

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000117

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

Jun 09, 2022

The c.904A>G (p.M302V) alteration is located in exon 10 (coding exon 8) of the SPATA21 gene. This alteration results from a A to G substitution at nucleotide position 904, causing the methionine (M) at amino acid position 302 to be replaced by a valine (V). 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

0.069

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.39

CADD

Benign

9.2

DANN

Benign

0.88

DEOGEN2

Benign

0.0045

.;T;.

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.047

LIST_S2

Benign

0.71

T;T;T

M_CAP

Benign

0.0096

MetaRNN

Benign

0.088

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.6

.;L;.

PrimateAI

Benign

0.31

PROVEAN

Uncertain

-2.6

D;N;N

REVEL

Benign

0.036

Sift

Benign

0.077

T;D;T

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

0.15

.;B;.

Vest4

0.14, 0.15

MutPred

0.40

.;Gain of loop (P = 3e-04);.;

MVP

0.21

MPC

0.093

ClinPred

0.088

GERP RS

1.3

Varity_R

0.36

gMVP

0.49

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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