rs17519417

Variant names:

• chr4-166738034-T-C
• rs17519417
• NM_001040159.2:c.995-430A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040159.2. 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
	SPOCK3	NM_001040159.2	MANE Select	c.995-430A>G		intron	N/A	NP_001035249.1	Q9BQ16-1
	SPOCK3	NM_016950.3		c.1004-430A>G		intron	N/A	NP_058646.2	Q9BQ16-3
	SPOCK3	NM_001430594.1		c.995-430A>G		intron	N/A	NP_001417523.1	Q9BQ16-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOCK3	ENST00000357545.9	TSL:1 MANE Select	c.995-430A>G		intron	N/A	ENSP00000350153.4	Q9BQ16-1
	SPOCK3	ENST00000502330.5	TSL:1	c.1004-430A>G		intron	N/A	ENSP00000423606.1	Q9BQ16-3
	SPOCK3	ENST00000357154.7	TSL:5	c.1004-430A>G		intron	N/A	ENSP00000349677.3	Q9BQ16-3

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

African (AFR) AF: 0.499 AC: 20668 AN: 41458

American (AMR) AF: 0.350 AC: 5343 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.560 AC: 1941 AN: 3464

East Asian (EAS) AF: 0.205 AC: 1061 AN: 5170

South Asian (SAS) AF: 0.457 AC: 2204 AN: 4822

European-Finnish (FIN) AF: 0.366 AC: 3875 AN: 10582

Middle Eastern (MID) AF: 0.415 AC: 122 AN: 294

European-Non Finnish (NFE) AF: 0.482 AC: 32780 AN: 67962

Other (OTH) AF: 0.472 AC: 998 AN: 2114

Alfa AF: 0.466 Hom.: 12463

Bravo AF: 0.453

Asia WGS AF: 0.320 AC: 1115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	7.1
DANN	Benign	0.53
PhyloP100		1.3
Mutation Taster		=100/0	polymorphism (auto)

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: rs17519417; hg19: chr4-167659185;