4-166997516-A-G

Variant names:

• chr4-166997516-A-G
• rs10517922
• NM_001040159.2:c.350+2833T>C

Variant summary

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

The NM_001040159.2(SPOCK3):​c.350+2833T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.197 in 152,066 control chromosomes in the GnomAD database, including 3,460 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 0.20 (3460 hom., cov: 32)
• Consequence: SPOCK3 NM_001040159.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• Publications: 1 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 = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOCK3	NM_001040159.2	c.350+2833T>C		intron_variant	Intron 4 of 10	ENST00000357545.9	NP_001035249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPOCK3	ENST00000357545.9	c.350+2833T>C		intron_variant	Intron 4 of 10	1	NM_001040159.2	ENSP00000350153.4

Frequencies

GnomAD3 genomes AF: 0.197 AC: 29915 AN: 151948 Hom.: 3455 Cov.: 32

Gnomad AFR AF: 0.323

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.140

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.0954

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.158

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

GnomAD4 genome AF: 0.197 AC: 29945 AN: 152066 Hom.: 3460 Cov.: 32 AF XY: 0.195 AC XY: 14535 AN XY: 74354

African (AFR) AF: 0.323 AC: 13378 AN: 41458

American (AMR) AF: 0.140 AC: 2139 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3470

East Asian (EAS) AF: 0.0956 AC: 494 AN: 5166

South Asian (SAS) AF: 0.182 AC: 876 AN: 4820

European-Finnish (FIN) AF: 0.148 AC: 1568 AN: 10602

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.155 AC: 10552 AN: 67980

Other (OTH) AF: 0.158 AC: 335 AN: 2114

Alfa AF: 0.187 Hom.: 360

Bravo AF: 0.198

Asia WGS AF: 0.143 AC: 496 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.2
DANN	Benign	0.79
PhyloP100		1.3
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: rs10517922; hg19: chr4-167918667;