chr5-95658912-G-A

Position:

• chr5-95658912-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_031952.4(SPATA9):​c.476C>T​(p.Ala159Val) variant causes a missense, splice region change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPATA9 NM_031952.4 missense, splice_region
• Scores: Splicing: ADA: 0.04108
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.71

Genes affected

SPATA9 (HGNC:22988): (spermatogenesis associated 9) Predicted to be involved in cell differentiation and spermatogenesis. Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

SPATA9 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16941366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPATA9	NM_031952.4	c.476C>T	p.Ala159Val	missense_variant, splice_region_variant	5/5	ENST00000274432.13	NP_114158.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPATA9	ENST00000274432.13	c.476C>T	p.Ala159Val	missense_variant, splice_region_variant	5/5	1	NM_031952.4	ENSP00000274432.8

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 21, 2024

The c.476C>T (p.A159V) alteration is located in exon 5 (coding exon 5) of the SPATA9 gene. This alteration results from a C to T substitution at nucleotide position 476, causing the alanine (A) at amino acid position 159 to be replaced by a valine (V). 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	0.24
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	T
Eigen	Benign	-0.016
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.66	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.0	M
PrimateAI	Benign	0.35	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.064
Sift	Uncertain	0.015	D
Sift4G	Uncertain	0.034	D
Polyphen		0.22	B
Vest4		0.27
MutPred		0.32		Gain of MoRF binding (P = 0.1974);
MVP		0.16
MPC		0.19
ClinPred		0.84	D
GERP RS		5.3
Varity_R		0.17
gMVP		0.36

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.041
dbscSNV1_RF	Benign	0.088
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

LitVar

Other links and lift over

dbSNP: rs752086093; hg19: chr5-94994616;