chr1-217782313-A-G

Variant names:

• chr1-217782313-A-G
• rs114098188
• NM_138796.4:c.863A>G

Variant summary

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

The NM_138796.4(SPATA17):​c.863A>G​(p.Asn288Ser) 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. 14/25 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: Not reported in ClinVar
• Conservation: PhyloP100: 2.00

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 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.863A>G	p.Asn288Ser	missense_variant	Exon 8 of 11	ENST00000366933.5	NP_620151.1
SPATA17	NM_001375655.1	c.863A>G	p.Asn288Ser	missense_variant	Exon 8 of 11		NP_001362584.1
SPATA17-AS1	NR_125784.1	n.160-14T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPATA17	ENST00000366933.5	c.863A>G	p.Asn288Ser	missense_variant	Exon 8 of 11	1	NM_138796.4	ENSP00000355900.4
SPATA17	ENST00000492747.2	n.709A>G		non_coding_transcript_exon_variant	Exon 5 of 6	5
SPATA17-AS1	ENST00000415765.1	n.160-14T>C		intron_variant	Intron 1 of 2	5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	14
DANN	Benign	0.48
DEOGEN2	Benign	0.016	T
Eigen	Benign	-0.81
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.012	T
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.045
Sift	Benign	0.64	T
Sift4G	Benign	0.61	T
Polyphen		0.024	B
Vest4		0.16
MutPred		0.24		Gain of helix (P = 0.0199);
MVP		0.25
MPC		0.022
ClinPred		0.055	T
GERP RS		2.4
Varity_R		0.055
gMVP		0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.70		Details are displayed if max score is > 0.2
DS_DG_spliceai		0.51		Position offset: -5
DS_DL_spliceai		0.70		Position offset: 9

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs114098188; hg19: chr1-217955655;