chr4-167229443-A-C

Position:

• chr4-167229443-A-C

Variant summary

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

The NM_001040159.2(SPOCK3):​c.189+4542T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.232 in 151,962 control chromosomes in the GnomAD database, including 4,854 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 0.23 (4854 hom., cov: 31)
• Consequence: SPOCK3 NM_001040159.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.05

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]

SPOCK3 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOCK3	NM_001040159.2	c.189+4542T>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.189+4542T>G		intron_variant		1	NM_001040159.2	ENSP00000350153.4

Frequencies

GnomAD3 genomes AF: 0.232 AC: 35229 AN: 151842 Hom.: 4850 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.0967

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.206

Gnomad SAS AF: 0.0911

Gnomad FIN AF: 0.0885

Gnomad MID AF: 0.207

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.250

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

GnomAD4 genome AF: 0.232 AC: 35271 AN: 151962 Hom.: 4854 Cov.: 31 AF XY: 0.228 AC XY: 16980 AN XY: 74314

Gnomad4 AFR AF: 0.383

Gnomad4 AMR AF: 0.290

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.205

Gnomad4 SAS AF: 0.0893

Gnomad4 FIN AF: 0.0885

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.248

Alfa AF: 0.168 Hom.: 918

Bravo AF: 0.259

Asia WGS AF: 0.165 AC: 574 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.3
DANN	Benign	0.66

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: rs1385513; hg19: chr4-168150594;