Variant 1-16400801-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.1093A>G(p.Asn365Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000248 in 1,611,330 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N365K) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.0000067 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SPATA21
NM_198546.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.567

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=0.092804104).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA21	NM_198546.1 linkuse as main transcript	c.1093A>G	p.Asn365Asp	missense_variant	11/13	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.1093A>G	p.Asn365Asp	missense_variant	11/13	1	NM_198546.1	ENSP00000335612.1	Q7Z572-1
SPATA21	ENST00000540400.1 linkuse as main transcript	c.1024A>G	p.Asn342Asp	missense_variant	9/11	1		ENSP00000440046.1	Q7Z572-2
SPATA21	ENST00000491418.5 linkuse as main transcript	c.217A>G	p.Asn73Asp	missense_variant	3/5	5		ENSP00000420753.1	H7C5T0
SPATA21	ENST00000466212.5 linkuse as main transcript	n.2385A>G		non_coding_transcript_exon_variant	13/17	2

Frequencies

GnomAD3 genomes

AF:

0.00000669

AC:

AN:

149446

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000663

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000120

AC:

AN:

250842

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135566

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000869

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000205

AC:

AN:

1461884

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000671

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000669

AC:

AN:

149446

Hom.:

Cov.:

AF XY:

0.0000137

AC XY:

AN XY:

73136

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000663

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

ExAC

AF:

0.0000165

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

Dec 03, 2021

The c.1093A>G (p.N365D) alteration is located in exon 11 (coding exon 9) of the SPATA21 gene. This alteration results from a A to G substitution at nucleotide position 1093, causing the asparagine (N) at amino acid position 365 to be replaced by an aspartic acid (D). 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

0.15

BayesDel_addAF

Benign

-0.11

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.97

DEOGEN2

Benign

0.013

.;T;.

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.81

FATHMM_MKL

Benign

0.068

LIST_S2

Benign

0.69

T;T;T

M_CAP

Benign

0.015

MetaRNN

Benign

0.093

T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.8

.;L;.

PrimateAI

Benign

0.37

PROVEAN

Uncertain

-3.0

D;D;D

REVEL

Benign

0.093

Sift

Benign

0.081

T;T;T

Sift4G

Benign

0.095

T;T;T

Polyphen

0.65

.;P;.

Vest4

0.33, 0.41

MutPred

0.18

.;Loss of MoRF binding (P = 0.107);.;

MVP

0.28

MPC

0.21

ClinPred

0.73

GERP RS

1.6

Varity_R

0.16

gMVP

0.23

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