4-166764062-C-T

Variant names:

• chr4-166764062-C-T
• rs7689440
• NM_001040159.2:c.710-9333G>A

Variant summary

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

The NM_001040159.2(SPOCK3):​c.710-9333G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 151,966 control chromosomes in the GnomAD database, including 4,072 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 0.21 (4072 hom., cov: 31)
• Consequence: SPOCK3 NM_001040159.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOCK3	NM_001040159.2	c.710-9333G>A		intron_variant	Intron 7 of 10	ENST00000357545.9	NP_001035249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPOCK3	ENST00000357545.9	c.710-9333G>A		intron_variant	Intron 7 of 10	1	NM_001040159.2	ENSP00000350153.4

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31666 AN: 151846 Hom.: 4062 Cov.: 31

Gnomad AFR AF: 0.0853

Gnomad AMI AF: 0.165

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.366

Gnomad EAS AF: 0.0672

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.224

Gnomad NFE AF: 0.288

Gnomad OTH AF: 0.229

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

GnomAD4 genome AF: 0.209 AC: 31686 AN: 151966 Hom.: 4072 Cov.: 31 AF XY: 0.206 AC XY: 15289 AN XY: 74274

Gnomad4 AFR AF: 0.0851

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.366

Gnomad4 EAS AF: 0.0671

Gnomad4 SAS AF: 0.301

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.288

Gnomad4 OTH AF: 0.237

Alfa AF: 0.281 Hom.: 12584

Bravo AF: 0.199

Asia WGS AF: 0.165 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.12

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: rs7689440; hg19: chr4-167685213;