17-3462717-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001170698.2(SPATA22):c.223G>A(p.Val75Met) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPATA22 NM_001170698.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.11

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 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=0.050841898).
• BP6: Variant 17-3462717-C-T is Benign according to our data. Variant chr17-3462717-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2260155.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPATA22	NM_001170698.2	c.223G>A	p.Val75Met	missense_variant	4/9	ENST00000572969.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPATA22	ENST00000572969.6	c.223G>A	p.Val75Met	missense_variant	4/9	1	NM_001170698.2	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 33

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 09, 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	0.062
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
Cadd	Benign	0.0020
Dann	Benign	0.89
DEOGEN2	Benign	0.0028	T;T;.;T;T;.;.;T;T;.;T;T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.0016	N
M_CAP	Benign	0.0062	T
MetaRNN	Benign	0.051	T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.18	N;N;.;N;N;.;N;.;.;.;.;.
MutationTaster	Benign	1.0	N;N;N;N;N;N;N
PrimateAI	Benign	0.34	T
PROVEAN	Benign	0.040	N;.;N;.;.;N;N;.;.;.;.;.
REVEL	Benign	0.067
Sift	Benign	0.37	T;.;T;.;.;T;T;.;.;.;.;.
Sift4G	Benign	0.26	T;T;T;T;T;T;T;.;.;.;T;T
Polyphen		0.0010	B;B;B;B;B;B;.;.;.;.;.;.
Vest4		0.11
MutPred		0.14		Gain of catalytic residue at V71 (P = 0.0263);Gain of catalytic residue at V71 (P = 0.0263);.;Gain of catalytic residue at V71 (P = 0.0263);Gain of catalytic residue at V71 (P = 0.0263);.;Gain of catalytic residue at V71 (P = 0.0263);.;.;.;Gain of catalytic residue at V71 (P = 0.0263);.;
MVP		0.18
MPC		0.027
ClinPred		0.20	T
GERP RS		-7.5
Varity_R		0.033
gMVP		0.072

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr17-3366011;