chr5-137067739-G-C

Position:

• chr5-137067739-G-C

Variant summary

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

The NM_004598.4(SPOCK1):​c.565C>G​(p.Pro189Ala) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: SPOCK1 NM_004598.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.44

Genes affected

SPOCK1 (HGNC:11251): (SPARC (osteonectin), cwcv and kazal like domains proteoglycan 1) This gene encodes the protein core of a seminal plasma proteoglycan containing chondroitin- and heparan-sulfate chains. The protein's function is unknown, although similarity to thyropin-type cysteine protease-inhibitors suggests its function may be related to protease inhibition. [provided by RefSeq, Jul 2008]

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=0.0885129).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOCK1	NM_004598.4	c.565C>G	p.Pro189Ala	missense_variant	6/11	ENST00000394945.6	NP_004589.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPOCK1	ENST00000394945.6	c.565C>G	p.Pro189Ala	missense_variant	6/11	1	NM_004598.4	ENSP00000378401	P1
SPOCK1	ENST00000510689.5	c.130C>G	p.Pro44Ala	missense_variant	5/6	4		ENSP00000421677
SPOCK1	ENST00000635347.1	n.538C>G		non_coding_transcript_exon_variant	6/7	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

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 28, 2022

The c.565C>G (p.P189A) alteration is located in exon 6 (coding exon 5) of the SPOCK1 gene. This alteration results from a C to G substitution at nucleotide position 565, causing the proline (P) at amino acid position 189 to be replaced by an alanine (A). 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	0.056
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	19
DANN	Benign	0.79
DEOGEN2	Benign	0.16	T;T;T
Eigen	Benign	-0.44
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.78	T;T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.089	T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N;.;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.35	T
PROVEAN	Benign	0.080	N;.;N
REVEL	Benign	0.032
Sift	Benign	0.45	T;.;T
Sift4G	Benign	0.60	T;T;T
Polyphen		0.0010	B;.;.
Vest4		0.23
MutPred		0.25		Loss of glycosylation at P189 (P = 0.0021);.;.;
MVP		0.35
MPC		0.24
ClinPred		0.45	T
GERP RS		4.8
Varity_R		0.063
gMVP		0.21

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: chr5-136403428;