5-137067787-C-A

Variant names:

• chr5-137067787-C-A
• rs139465331
• NM_004598.4:c.517G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004598.4(SPOCK1):​c.517G>T​(p.Ala173Ser) 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. 16/22 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. A173T) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: SPOCK1 NM_004598.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 9 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028131872).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004598.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOCK1	NM_004598.4	MANE Select	c.517G>T	p.Ala173Ser	missense	Exon 6 of 11	NP_004589.1	Q08629

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOCK1	ENST00000394945.6	TSL:1 MANE Select	c.517G>T	p.Ala173Ser	missense	Exon 6 of 11	ENSP00000378401.1	Q08629
	SPOCK1	ENST00000510689.5	TSL:4	c.82G>T	p.Ala28Ser	missense	Exon 5 of 6	ENSP00000421677.1	D6RAM7
	SPOCK1	ENST00000635347.1	TSL:5	n.490G>T		non_coding_transcript_exon	Exon 6 of 7

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251480 AF XY: 0.00000736

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000163

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.061
BayesDel_addAF	Benign	-0.39	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	7.7
DANN	Benign	0.78
DEOGEN2	Benign	0.059	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.054	T
M_CAP	Benign	0.0084	T
MetaRNN	Benign	0.028	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	-1.9	N
PhyloP100		0.097
PrimateAI	Benign	0.32	T
PROVEAN	Benign	0.90	N
REVEL	Benign	0.024
Sift	Benign	1.0	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.37		Loss of phosphorylation at T168 (P = 0.2011)
MVP		0.14
MPC		0.22
ClinPred		0.043	T
GERP RS		1.5
Varity_R		0.023
gMVP		0.14
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

dbSNP: rs139465331; hg19: chr5-136403476;