17-3462522-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001170698.2(SPATA22):c.290C>G(p.Ser97Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 33)
• Consequence: SPATA22 NM_001170698.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.475

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]

ACMG classification

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=0.0817875).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA22	NM_001170698.2	c.290C>G	p.Ser97Cys	missense_variant	5/9	ENST00000572969.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA22	ENST00000572969.6	c.290C>G	p.Ser97Cys	missense_variant	5/9	1	NM_001170698.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 18, 2023

The c.290C>G (p.S97C) alteration is located in exon 5 (coding exon 4) of the SPATA22 gene. This alteration results from a C to G substitution at nucleotide position 290, causing the serine (S) at amino acid position 97 to be replaced by a cysteine (C). 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	0.080
BayesDel_addAF	Benign	-0.17	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	12
Dann	Benign	0.73
DEOGEN2	Benign	0.050	T;T;.;T;T;.;.;T;T;.;T;T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.83
FATHMM_MKL	Benign	0.094	N
M_CAP	Benign	0.0025	T
MetaRNN	Benign	0.082	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.6	L;L;.;L;L;.;L;.;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.2	N;.;D;.;.;N;D;.;.;.;.;.
REVEL	Benign	0.054
Sift	Benign	0.047	D;.;T;.;.;D;D;.;.;.;.;.
Sift4G	Uncertain	0.033	D;D;D;D;D;D;T;.;.;.;D;D
Polyphen		0.0090	B;B;B;B;B;B;.;.;.;.;.;.
Vest4		0.14
MutPred		0.22		Loss of disorder (P = 0.0098);Loss of disorder (P = 0.0098);.;Loss of disorder (P = 0.0098);Loss of disorder (P = 0.0098);.;Loss of disorder (P = 0.0098);.;.;.;Loss of disorder (P = 0.0098);.;
MVP		0.061
MPC		0.027
ClinPred		0.062	T
GERP RS		1.1
Varity_R		0.079
gMVP		0.26

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-3365816; COSMIC: COSV52152042; COSMIC: COSV52152042;