rs17519417

Positions:

• chr4-166738034-T-C

Variant summary

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

The NM_001040159.2(SPOCK3):​c.995-430A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 152,044 control chromosomes in the GnomAD database, including 16,331 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 0.46 (16331 hom., cov: 32)
• Consequence: SPOCK3 NM_001040159.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31

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=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOCK3	NM_001040159.2	c.995-430A>G		intron_variant		ENST00000357545.9	NP_001035249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPOCK3	ENST00000357545.9	c.995-430A>G		intron_variant		1	NM_001040159.2	ENSP00000350153	A2

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69326 AN: 151926 Hom.: 16314 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.351

Gnomad ASJ AF: 0.560

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.457

Gnomad FIN AF: 0.366

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.482

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.456 AC: 69384 AN: 152044 Hom.: 16331 Cov.: 32 AF XY: 0.448 AC XY: 33300 AN XY: 74304

Gnomad4 AFR AF: 0.499

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.560

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.457

Gnomad4 FIN AF: 0.366

Gnomad4 NFE AF: 0.482

Gnomad4 OTH AF: 0.472

Alfa AF: 0.470 Hom.: 8897

Bravo AF: 0.453

Asia WGS AF: 0.320 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.53

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: rs17519417; hg19: chr4-167659185;