Variant 17-3449123-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001170698.2(SPATA22):c.356G>A(p.Ser119Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000687 in 1,455,214 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

SPATA22
NM_001170698.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.318

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.063922495).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA22	NM_001170698.2 linkuse as main transcript	c.356G>A	p.Ser119Asn	missense_variant	6/9	ENST00000572969.6	NP_001164169.1	Q8NHS9-1A0A140VJV9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA22	ENST00000572969.6 linkuse as main transcript	c.356G>A	p.Ser119Asn	missense_variant	6/9	1	NM_001170698.2	ENSP00000460187.1		Q8NHS9-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000406

AC:

AN:

246106

Hom.:

AF XY:

0.00000752

AC XY:

AN XY:

133034

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:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000892

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.87e-7

AC:

AN:

1455214

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

723656

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.01e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

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

Aug 26, 2024

The c.356G>A (p.S119N) alteration is located in exon 6 (coding exon 5) of the SPATA22 gene. This alteration results from a G to A substitution at nucleotide position 356, causing the serine (S) at amino acid position 119 to be replaced by an asparagine (N). 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

0.084

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.75

CADD

Benign

6.6

DANN

Benign

0.91

DEOGEN2

Benign

0.0052

T;T;.;T;T;.;.;T;T;.;T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.60

.;.;T;.;T;T;T;T;T;T;T;T

M_CAP

Benign

0.0055

MetaRNN

Benign

0.064

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.4

L;L;.;L;L;.;L;.;.;.;.;.

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.6

N;.;N;.;.;N;N;.;.;.;.;.

REVEL

Benign

0.038

Sift

Benign

0.11

T;.;T;.;.;T;T;.;.;.;.;.

Sift4G

Benign

0.30

T;T;T;T;T;T;T;.;.;.;T;T

Polyphen

0.0030

B;B;B;B;B;B;.;.;.;.;.;.

Vest4

0.13

MutPred

0.086

Gain of methylation at K121 (P = 0.152);Gain of methylation at K121 (P = 0.152);.;Gain of methylation at K121 (P = 0.152);Gain of methylation at K121 (P = 0.152);.;Gain of methylation at K121 (P = 0.152);.;.;.;Gain of methylation at K121 (P = 0.152);.;

MVP

0.048

MPC

0.026

ClinPred

0.031

GERP RS

1.3

Varity_R

0.068

gMVP

0.25

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