17-3446526-T-C

Variant names:

• chr17-3446526-T-C
• rs1440315271
• NM_001170698.2:c.748A>G

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001170698.2(SPATA22):​c.748A>G​(p.Met250Val) 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. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M250L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA22 NM_001170698.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.83
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• infertility disorder

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.14722773).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001170698.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA22	NM_001170698.2	MANE Select	c.748A>G	p.Met250Val	missense	Exon 7 of 9	NP_001164169.1	Q8NHS9-1
	SPATA22	NM_001170695.2		c.748A>G	p.Met250Val	missense	Exon 7 of 9	NP_001164166.1	Q8NHS9-1
	SPATA22	NM_001170697.2		c.748A>G	p.Met250Val	missense	Exon 7 of 9	NP_001164168.1	Q8NHS9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPATA22	ENST00000572969.6	TSL:1 MANE Select	c.748A>G	p.Met250Val	missense	Exon 7 of 9	ENSP00000460187.1	Q8NHS9-1
	SPATA22	ENST00000397168.7	TSL:1	c.748A>G	p.Met250Val	missense	Exon 7 of 9	ENSP00000380354.3	Q8NHS9-1
	SPATA22	ENST00000573128.5	TSL:1	c.748A>G	p.Met250Val	missense	Exon 7 of 9	ENSP00000459580.1	Q8NHS9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.074	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.052	T
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.27
FATHMM_MKL	Uncertain	0.84	D
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.9	L
PhyloP100		2.8
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-2.0	N
REVEL	Benign	0.077
Sift	Benign	0.18	T
Sift4G	Benign	0.18	T
Polyphen		0.0	B
Vest4		0.40
MutPred		0.27		Gain of methylation at K251 (P = 0.0179)
MVP		0.58
MPC		0.027
ClinPred		0.46	T
GERP RS		3.0
Varity_R		0.12
gMVP		0.55

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

Other links and lift over

dbSNP: rs1440315271; hg19: chr17-3349820;