NM_001040159.2:c.710-9333G>A

Variant names:

• chr4-166764062-C-T
• rs7689440
• NM_001040159.2:c.710-9333G>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.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
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.288 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOCK3	NM_001040159.2	MANE Select	c.710-9333G>A		intron	N/A	NP_001035249.1
	SPOCK3	NM_016950.3		c.719-9333G>A		intron	N/A	NP_058646.2
	SPOCK3	NM_001430594.1		c.710-9333G>A		intron	N/A	NP_001417523.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SPOCK3	ENST00000357545.9	TSL:1 MANE Select	c.710-9333G>A		intron	N/A	ENSP00000350153.4
	SPOCK3	ENST00000502330.5	TSL:1	c.719-9333G>A		intron	N/A	ENSP00000423606.1
	SPOCK3	ENST00000512648.5	TSL:1	c.710-9333G>A		intron	N/A	ENSP00000426177.1

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

African (AFR) AF: 0.0851 AC: 3532 AN: 41490

American (AMR) AF: 0.187 AC: 2843 AN: 15238

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 1270 AN: 3466

East Asian (EAS) AF: 0.0671 AC: 345 AN: 5140

South Asian (SAS) AF: 0.301 AC: 1453 AN: 4826

European-Finnish (FIN) AF: 0.186 AC: 1972 AN: 10574

Middle Eastern (MID) AF: 0.231 AC: 67 AN: 290

European-Non Finnish (NFE) AF: 0.288 AC: 19554 AN: 67924

Other (OTH) AF: 0.237 AC: 500 AN: 2108

Alfa AF: 0.265 Hom.: 17889

Bravo AF: 0.199

Asia WGS AF: 0.165 AC: 575 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.2
DANN	Benign	0.12
PhyloP100		-0.76
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: rs7689440; hg19: chr4-167685213;