1-217669078-G-C

Variant names:

• chr1-217669078-G-C
• NM_138796.4:c.286G>C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_138796.4(SPATA17):​c.286G>C​(p.Val96Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA17 NM_138796.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.18

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPATA17	NM_138796.4	c.286G>C	p.Val96Leu	missense_variant	Exon 4 of 11	ENST00000366933.5	NP_620151.1
SPATA17	NM_001375655.1	c.286G>C	p.Val96Leu	missense_variant	Exon 4 of 11		NP_001362584.1
SPATA17	XM_011509194.4	c.286G>C	p.Val96Leu	missense_variant	Exon 4 of 7		XP_011507496.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA17	ENST00000366933.5	c.286G>C	p.Val96Leu	missense_variant	Exon 4 of 11	1	NM_138796.4	ENSP00000355900.4
SPATA17	ENST00000470448.5	n.*229G>C		non_coding_transcript_exon_variant	Exon 5 of 8	3		ENSP00000473514.1
SPATA17	ENST00000470448.5	n.*229G>C		3_prime_UTR_variant	Exon 5 of 8	3		ENSP00000473514.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Feb 22, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.286G>C (p.V96L) alteration is located in exon 4 (coding exon 4) of the SPATA17 gene. This alteration results from a G to C substitution at nucleotide position 286, causing the valine (V) at amino acid position 96 to be replaced by a leucine (L). 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	Uncertain	0.47
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.040
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.038	T
Eigen	Pathogenic	0.93
Eigen_PC	Pathogenic	0.92
FATHMM_MKL	Pathogenic	1.0	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.026	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Uncertain	2.8	M
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.011	D
Polyphen		1.0	D
Vest4		0.83
MutPred		0.57		Loss of catalytic residue at V96 (P = 0.0946);
MVP		0.25
MPC		0.19
ClinPred		0.97	D
GERP RS		5.8
Varity_R		0.43
gMVP		0.71

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-217842420;