rs771892496

Variant names:

• chr17-3449123-C-T
• rs771892496
• NM_001170698.2:c.356G>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_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. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SPATA22 NM_001170698.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.318
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.063922495).

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.356G>A	p.Ser119Asn	missense	Exon 6 of 9	NP_001164169.1	Q8NHS9-1
	SPATA22	NM_001170695.2		c.356G>A	p.Ser119Asn	missense	Exon 6 of 9	NP_001164166.1	Q8NHS9-1
	SPATA22	NM_001170697.2		c.356G>A	p.Ser119Asn	missense	Exon 6 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.356G>A	p.Ser119Asn	missense	Exon 6 of 9	ENSP00000460187.1	Q8NHS9-1
	SPATA22	ENST00000397168.7	TSL:1	c.356G>A	p.Ser119Asn	missense	Exon 6 of 9	ENSP00000380354.3	Q8NHS9-1
	SPATA22	ENST00000573128.5	TSL:1	c.356G>A	p.Ser119Asn	missense	Exon 6 of 9	ENSP00000459580.1	Q8NHS9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000406 AC: 1 AN: 246106 AF XY: 0.00000752

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000892

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1455214 Hom.: 0 Cov.: 34 AF XY: 0.00000138 AC XY: 1 AN XY: 723656

African (AFR) AF: 0.00 AC: 0 AN: 33030

American (AMR) AF: 0.00 AC: 0 AN: 43286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25906

East Asian (EAS) AF: 0.00 AC: 0 AN: 39594

South Asian (SAS) AF: 0.00 AC: 0 AN: 84804

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5738

European-Non Finnish (NFE) AF: 9.01e-7 AC: 1 AN: 1109544

Other (OTH) AF: 0.00 AC: 0 AN: 60074

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.75
CADD	Benign	6.6
DANN	Benign	0.91
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.60	T
M_CAP	Benign	0.0055	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.32
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.038
Sift	Benign	0.11	T
Sift4G	Benign	0.30	T
Polyphen		0.0030	B
Vest4		0.13
MutPred		0.086		Gain of methylation at K121 (P = 0.152)
MVP		0.048
MPC		0.026
ClinPred		0.031	T
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

Other links and lift over

dbSNP: rs771892496; hg19: chr17-3352417;