NM_001040159.2:c.189+955G>A

Variant names:

• chr4-167233030-C-T
• rs7657608
• NM_001040159.2:c.189+955G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040159.2(SPOCK3):​c.189+955G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.305 in 152,018 control chromosomes in the GnomAD database, including 7,267 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 0.30 (7267 hom., cov: 32)
• Consequence: SPOCK3 NM_001040159.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900
• Publications: 7 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.332 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOCK3	NM_001040159.2	c.189+955G>A		intron_variant	Intron 2 of 10	ENST00000357545.9	NP_001035249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPOCK3	ENST00000357545.9	c.189+955G>A		intron_variant	Intron 2 of 10	1	NM_001040159.2	ENSP00000350153.4

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46247 AN: 151900 Hom.: 7255 Cov.: 32

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.451

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.329

Gnomad FIN AF: 0.256

Gnomad MID AF: 0.168

Gnomad NFE AF: 0.321

Gnomad OTH AF: 0.290

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

GnomAD4 genome AF: 0.305 AC: 46295 AN: 152018 Hom.: 7267 Cov.: 32 AF XY: 0.300 AC XY: 22283 AN XY: 74280

African (AFR) AF: 0.337 AC: 13984 AN: 41474

American (AMR) AF: 0.243 AC: 3719 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.247 AC: 856 AN: 3468

East Asian (EAS) AF: 0.116 AC: 601 AN: 5166

South Asian (SAS) AF: 0.328 AC: 1580 AN: 4810

European-Finnish (FIN) AF: 0.256 AC: 2701 AN: 10546

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.321 AC: 21791 AN: 67952

Other (OTH) AF: 0.287 AC: 604 AN: 2108

Alfa AF: 0.285 Hom.: 7089

Bravo AF: 0.301

Asia WGS AF: 0.219 AC: 762 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.50
DANN	Benign	0.71
PhyloP100		-0.90
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: rs7657608; hg19: chr4-168154181;