17-3446535-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001170698.2(SPATA22):c.739A>G(p.Ile247Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA22 NM_001170698.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.55

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.32090712).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA22	NM_001170698.2	c.739A>G	p.Ile247Val	missense_variant	7/9	ENST00000572969.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA22	ENST00000572969.6	c.739A>G	p.Ile247Val	missense_variant	7/9	1	NM_001170698.2	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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

Jan 16, 2024

The c.739A>G (p.I247V) alteration is located in exon 7 (coding exon 6) of the SPATA22 gene. This alteration results from a A to G substitution at nucleotide position 739, causing the isoleucine (I) at amino acid position 247 to be replaced by a valine (V). 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	0.20
BayesDel_addAF	Uncertain	0.048	T
BayesDel_noAF	Benign	-0.17
Cadd	Uncertain	24
Dann	Uncertain	1.0
DEOGEN2	Benign	0.048	T;T;.;T;T;.;.
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.49
FATHMM_MKL	Uncertain	0.95	D
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.32	T;T;T;T;T;T;T
MetaSVM	Uncertain	-0.019	T
MutationAssessor	Benign	1.9	L;L;.;L;L;.;L
MutationTaster	Benign	0.77	N;N;N;N;N;N;N
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.74	N;.;N;.;.;N;N
REVEL	Benign	0.20
Sift	Benign	0.12	T;.;T;.;.;T;D
Sift4G	Pathogenic	0.0	D;D;D;D;D;D;D
Polyphen		0.99	D;D;P;D;D;P;.
Vest4		0.41
MutPred		0.20		Gain of MoRF binding (P = 0.1007);Gain of MoRF binding (P = 0.1007);.;Gain of MoRF binding (P = 0.1007);Gain of MoRF binding (P = 0.1007);.;Gain of MoRF binding (P = 0.1007);
MVP		0.63
MPC		0.036
ClinPred		0.83	D
GERP RS		5.3
Varity_R		0.13
gMVP		0.36

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: chr17-3349829;