1-217782314-T-A

Variant names:

• chr1-217782314-T-A
• NM_138796.4:c.864T>A

Variant summary

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

The NM_138796.4(SPATA17):​c.864T>A​(p.Asn288Lys) 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. 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. N288I) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA17 NM_138796.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.547

Genes affected

SPATA17 (HGNC:25184): (spermatogenesis associated 17) Predicted to enable calmodulin binding activity. Predicted to be located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

SPATA17-AS1 (HGNC:41086): (SPATA17 antisense RNA 1)

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.06354329).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA17	NM_138796.4	c.864T>A	p.Asn288Lys	missense_variant	Exon 8 of 11	ENST00000366933.5	NP_620151.1
SPATA17	NM_001375655.1	c.864T>A	p.Asn288Lys	missense_variant	Exon 8 of 11		NP_001362584.1
SPATA17-AS1	NR_125784.1	n.160-15A>T		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA17	ENST00000366933.5	c.864T>A	p.Asn288Lys	missense_variant	Exon 8 of 11	1	NM_138796.4	ENSP00000355900.4
SPATA17	ENST00000492747.2	n.710T>A		non_coding_transcript_exon_variant	Exon 5 of 6	5
SPATA17-AS1	ENST00000415765.1	n.160-15A>T		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 19, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.864T>A (p.N288K) alteration is located in exon 8 (coding exon 8) of the SPATA17 gene. This alteration results from a T to A substitution at nucleotide position 864, causing the asparagine (N) at amino acid position 288 to be replaced by a lysine (K). 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	Benign	-0.34	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	0.054
DANN	Benign	0.40
DEOGEN2	Benign	0.043	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.064	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.025
Sift	Benign	0.33	T
Sift4G	Benign	0.56	T
Polyphen		0.48	P
Vest4		0.27
MutPred		0.33		Gain of methylation at N288 (P = 0.0101);
MVP		0.14
MPC		0.040
ClinPred		0.15	T
GERP RS		-9.5
Varity_R		0.081
gMVP		0.41

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: chr1-217955656;