chr17-3467489-G-A

Variant names:

• chr17-3467489-G-A
• rs145051415
• NM_001170698.2:c.109C>T

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.109C>T​(p.Leu37Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. L37V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: SPATA22 NM_001170698.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.21
• 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=0.18801248).

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.109C>T	p.Leu37Phe	missense	Exon 3 of 9	NP_001164169.1	Q8NHS9-1
	SPATA22	NM_001170695.2		c.109C>T	p.Leu37Phe	missense	Exon 3 of 9	NP_001164166.1	Q8NHS9-1
	SPATA22	NM_001170697.2		c.109C>T	p.Leu37Phe	missense	Exon 3 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.109C>T	p.Leu37Phe	missense	Exon 3 of 9	ENSP00000460187.1	Q8NHS9-1
	SPATA22	ENST00000397168.7	TSL:1	c.109C>T	p.Leu37Phe	missense	Exon 3 of 9	ENSP00000380354.3	Q8NHS9-1
	SPATA22	ENST00000573128.5	TSL:1	c.109C>T	p.Leu37Phe	missense	Exon 3 of 9	ENSP00000459580.1	Q8NHS9-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 250304 AF XY: 0.00

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: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458516 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 725454

African (AFR) AF: 0.00 AC: 0 AN: 33394

American (AMR) AF: 0.00 AC: 0 AN: 44542

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26066

East Asian (EAS) AF: 0.00 AC: 0 AN: 39434

South Asian (SAS) AF: 0.0000117 AC: 1 AN: 85548

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53272

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1110308

Other (OTH) AF: 0.00 AC: 0 AN: 60214

GnomAD4 genome Cov.: 32

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.10	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.36
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.19	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		2.2
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-1.6	N
REVEL	Benign	0.13
Sift	Uncertain	0.0070	D
Sift4G	Benign	0.068	T
Polyphen		0.99	D
Vest4		0.25
MutPred		0.11		Loss of catalytic residue at L37 (P = 0.0314)
MVP		0.40
MPC		0.037
ClinPred		0.66	D
GERP RS		3.9
Varity_R		0.12
gMVP		0.14

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: rs145051415; hg19: chr17-3370783;