Variant 1-16400765-G-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.1129C>G(p.Arg377Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000205 in 1,461,870 control chromosomes in the GnomAD database, including 1 homozygotes. 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: 32)

Exomes 𝑓: 0.000021 ( 1 hom. )

Consequence

SPATA21
NM_198546.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.32

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=0.13606584).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA21	NM_198546.1 linkuse as main transcript	c.1129C>G	p.Arg377Gly	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.1129C>G	p.Arg377Gly	missense_variant	11/13	1	NM_198546.1	ENSP00000335612.1	Q7Z572-1
SPATA21	ENST00000540400.1 linkuse as main transcript	c.1060C>G	p.Arg354Gly	missense_variant	9/11	1		ENSP00000440046.1	Q7Z572-2
SPATA21	ENST00000491418.5 linkuse as main transcript	c.253C>G	p.Arg85Gly	missense_variant	3/5	5		ENSP00000420753.1	H7C5T0
SPATA21	ENST00000466212.5 linkuse as main transcript	n.2421C>G		non_coding_transcript_exon_variant	13/17	2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000199

AC:

AN:

251448

Hom.:

AF XY:

0.0000221

AC XY:

AN XY:

135894

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:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000205

AC:

AN:

1461870

Hom.:

Cov.:

AF XY:

0.0000220

AC XY:

AN XY:

727240

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:

0.000162

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000144

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Oct 25, 2022

The c.1129C>G (p.R377G) alteration is located in exon 11 (coding exon 9) of the SPATA21 gene. This alteration results from a C to G substitution at nucleotide position 1129, causing the arginine (R) at amino acid position 377 to be replaced by a glycine (G). 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

-0.17

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.027

.;T;.

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.72

LIST_S2

Benign

0.70

T;T;T

M_CAP

Benign

0.021

MetaRNN

Benign

0.14

T;T;T

MetaSVM

Benign

-0.70

MutationAssessor

Benign

1.5

.;L;.

PrimateAI

Benign

0.32

PROVEAN

Pathogenic

-5.2

D;D;D

REVEL

Benign

0.055

Sift

Benign

0.052

T;T;T

Sift4G

Benign

0.089

T;T;T

Polyphen

0.015

.;B;.

Vest4

0.26, 0.29

MutPred

0.32

.;Loss of helix (P = 0.0068);.;

MVP

0.41

MPC

0.17

ClinPred

0.89

GERP RS

3.0

Varity_R

0.23

gMVP

0.25

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