rs9312517

Positions:

• chr4-167218229-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040159.2(SPOCK3):​c.189+15756T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,088 control chromosomes in the GnomAD database, including 1,702 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1702 hom., cov: 32)
• Consequence: SPOCK3 NM_001040159.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0110

Genes affected

SPOCK3 (HGNC:13565): (SPARC (osteonectin), cwcv and kazal like domains proteoglycan 3) This gene encodes a member of a novel family of calcium-binding proteoglycan proteins that contain thyroglobulin type-1 and Kazal-like domains. The encoded protein and may play a role in adult T-cell leukemia by inhibiting the activity of membrane-type matrix metalloproteinases. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOCK3	NM_001040159.2	c.189+15756T>C		intron_variant		ENST00000357545.9	NP_001035249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPOCK3	ENST00000357545.9	c.189+15756T>C		intron_variant		1	NM_001040159.2	ENSP00000350153	A2

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20336 AN: 151970 Hom.: 1698 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.0495

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.201

Gnomad SAS AF: 0.0452

Gnomad FIN AF: 0.0520

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0860

Gnomad OTH AF: 0.153

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.134 AC: 20367 AN: 152088 Hom.: 1702 Cov.: 32 AF XY: 0.133 AC XY: 9870 AN XY: 74344

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.112

Gnomad4 EAS AF: 0.201

Gnomad4 SAS AF: 0.0440

Gnomad4 FIN AF: 0.0520

Gnomad4 NFE AF: 0.0860

Gnomad4 OTH AF: 0.152

Alfa AF: 0.103 Hom.: 1906

Bravo AF: 0.153

Asia WGS AF: 0.134 AC: 465 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.0
DANN	Benign	0.29

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

LitVar

Other links and lift over

dbSNP: rs9312517; hg19: chr4-168139380;