Variant 17-3467452-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001170698.2(SPATA22):c.146A>G(p.Asn49Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000129 in 1,602,346 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

SPATA22
NM_001170698.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.304

Variant links:

Genes affected

SPATA22 (HGNC:30705): (spermatogenesis associated 22) Predicted to be involved in regulation of meiotic cell cycle. Predicted to act upstream of or within several processes, including fertilization; gamete generation; and meiosis I cell cycle process. Predicted to be located in chromosome. [provided by Alliance of Genome Resources, Apr 2022]

SPATA22 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.051915646).

BP6

Variant 17-3467452-T-C is Benign according to our data. Variant chr17-3467452-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2341388.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA22	NM_001170698.2 linkuse as main transcript	c.146A>G	p.Asn49Ser	missense_variant	3/9	ENST00000572969.6	NP_001164169.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA22	ENST00000572969.6 linkuse as main transcript	c.146A>G	p.Asn49Ser	missense_variant	3/9	1	NM_001170698.2	ENSP00000460187	P1	Q8NHS9-1

Frequencies

GnomAD3 genomes

AF:

0.0000328

AC:

AN:

152208

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000655

AC:

AN:

244112

Hom.:

AF XY:

0.0000455

AC XY:

AN XY:

131974

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000123

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:

0.000108

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000139

AC:

202

AN:

1450138

Hom.:

Cov.:

AF XY:

0.000117

AC XY:

AN XY:

720700

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000162

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:

0.000176

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000328

AC:

AN:

152208

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000535

Hom.:

Bravo

AF:

0.0000680

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 23, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.058

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.31

DANN

Benign

0.76

DEOGEN2

Benign

0.0037

T;T;T;T;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-0.95

FATHMM_MKL

Benign

0.049

LIST_S2

Benign

0.65

.;.;.;T;T;T

M_CAP

Benign

0.0041

MetaRNN

Benign

0.052

T;T;T;T;T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

-0.58

N;N;N;N;N;.

MutationTaster

Benign

1.0

D;D;N;N;N;N;N

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.25

N;.;.;.;N;.

REVEL

Benign

0.028

Sift

Benign

0.89

T;.;.;.;T;.

Sift4G

Benign

1.0

T;T;T;T;T;T

Polyphen

0.0010

B;B;B;B;.;.

Vest4

0.14

MVP

0.030

MPC

0.024

ClinPred

0.024

GERP RS

-0.50

Varity_R

0.025

gMVP

0.085

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