rs897511

Positions:

• chr4-166774510-T-G

Variant summary

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

The NM_001040159.2(SPOCK3):​c.709+17660A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.407 in 152,066 control chromosomes in the GnomAD database, including 13,277 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 0.41 (13277 hom., cov: 32)
• Consequence: SPOCK3 NM_001040159.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0870

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.507 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPOCK3	NM_001040159.2	c.709+17660A>C		intron_variant		ENST00000357545.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPOCK3	ENST00000357545.9	c.709+17660A>C		intron_variant		1	NM_001040159.2	A2

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61783 AN: 151948 Hom.: 13261 Cov.: 32

Gnomad AFR AF: 0.513

Gnomad AMI AF: 0.393

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.488

Gnomad EAS AF: 0.134

Gnomad SAS AF: 0.418

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.403

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

GnomAD4 genome AF: 0.407 AC: 61842 AN: 152066 Hom.: 13277 Cov.: 32 AF XY: 0.399 AC XY: 29642 AN XY: 74324

Gnomad4 AFR AF: 0.513

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.488

Gnomad4 EAS AF: 0.135

Gnomad4 SAS AF: 0.417

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.399

Gnomad4 OTH AF: 0.406

Alfa AF: 0.398 Hom.: 16279

Bravo AF: 0.406

Asia WGS AF: 0.262 AC: 914 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.2
DANN	Benign	0.70

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: rs897511; hg19: chr4-167695661;