9-132888386-G-T

Position:

• chr9-132888386-G-T

Variant summary

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

The NM_001316897.2(SPACA9):​c.444G>T​(p.Met148Ile) 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. 12/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPACA9 NM_001316897.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.76

Genes affected

SPACA9 (HGNC:1367): (sperm acrosome associated 9) Predicted to enable calcium-dependent protein binding activity. Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

SPACA9 (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=0.11180124).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPACA9	NM_001316897.2	c.444G>T	p.Met148Ile	missense_variant	4/4	ENST00000356311.10	NP_001303826.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPACA9	ENST00000356311.10	c.444G>T	p.Met148Ile	missense_variant	4/4	2	NM_001316897.2	ENSP00000348659.5
SPACA9	ENST00000372136.7	c.444G>T	p.Met148Ile	missense_variant	4/4	1		ENSP00000361209.3
SPACA9	ENST00000350499.6	c.444G>T	p.Met148Ile	missense_variant	4/5	1		ENSP00000298546.7

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

Jul 20, 2021

The c.444G>T (p.M148I) alteration is located in exon 4 (coding exon 3) of the SPACA9 gene. This alteration results from a G to T substitution at nucleotide position 444, causing the methionine (M) at amino acid position 148 to be replaced by an isoleucine (I). 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	Pathogenic	0.79
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	21
DANN	Benign	0.97
DEOGEN2	Benign	0.033	T;T;.
Eigen	Benign	-0.071
Eigen_PC	Benign	0.065
FATHMM_MKL	Uncertain	0.78	D
LIST_S2	Benign	0.74	.;T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.11	T;T;T
MetaSVM	Benign	-0.97	T
PROVEAN	Benign	-0.65	N;N;N
REVEL	Benign	0.059
Sift	Benign	0.27	T;T;T
Sift4G	Benign	0.34	T;T;T
Polyphen		0.25	B;B;B
Vest4		0.19
MutPred		0.33		Gain of methylation at K149 (P = 0.0228);Gain of methylation at K149 (P = 0.0228);Gain of methylation at K149 (P = 0.0228);
MVP		0.32
MPC		0.094
ClinPred		0.67	D
GERP RS		5.2
Varity_R		0.19
gMVP		0.50

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: chr9-135763773;