chr4-166920133-C-T

Variant names:

• chr4-166920133-C-T
• rs17052671
• NM_001040159.2:c.351-7390G>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.351-7390G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,978 control chromosomes in the GnomAD database, including 6,859 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 0.29 (6859 hom., cov: 32)
• Consequence: SPOCK3 NM_001040159.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.04
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 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.351-7390G>A		intron	N/A	NP_001035249.1	Q9BQ16-1
	SPOCK3	NM_016950.3		c.360-7390G>A		intron	N/A	NP_058646.2	Q9BQ16-3
	SPOCK3	NM_001430594.1		c.351-7390G>A		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.351-7390G>A		intron	N/A	ENSP00000350153.4	Q9BQ16-1
	SPOCK3	ENST00000502330.5	TSL:1	c.360-7390G>A		intron	N/A	ENSP00000423606.1	Q9BQ16-3
	SPOCK3	ENST00000512648.5	TSL:1	c.351-7390G>A		intron	N/A	ENSP00000426177.1	Q9BQ16-9

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44280 AN: 151860 Hom.: 6846 Cov.: 32

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.295

Gnomad AMR AF: 0.224

Gnomad ASJ AF: 0.468

Gnomad EAS AF: 0.0362

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.267

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.308

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

GnomAD4 genome AF: 0.292 AC: 44325 AN: 151978 Hom.: 6859 Cov.: 32 AF XY: 0.286 AC XY: 21269 AN XY: 74256

African (AFR) AF: 0.260 AC: 10774 AN: 41460

American (AMR) AF: 0.223 AC: 3407 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.468 AC: 1626 AN: 3472

East Asian (EAS) AF: 0.0363 AC: 188 AN: 5182

South Asian (SAS) AF: 0.309 AC: 1491 AN: 4820

European-Finnish (FIN) AF: 0.267 AC: 2813 AN: 10532

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23009 AN: 67936

Other (OTH) AF: 0.314 AC: 662 AN: 2106

Alfa AF: 0.310 Hom.: 14010

Bravo AF: 0.286

Asia WGS AF: 0.197 AC: 687 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.18
DANN	Benign	0.62
PhyloP100		-1.0
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: rs17052671; hg19: chr4-167841284;