Variant 4-166742020-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001040159.2(SPOCK3):c.971G>A(p.Arg324Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000781 in 1,612,770 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

SPOCK3
NM_001040159.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.48

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02345571).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOCK3	NM_001040159.2 linkuse as main transcript	c.971G>A	p.Arg324Gln	missense_variant	9/11	ENST00000357545.9	NP_001035249.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SPOCK3	ENST00000357545.9 linkuse as main transcript	c.971G>A	p.Arg324Gln	missense_variant	9/11	1	NM_001040159.2	ENSP00000350153	A2	Q9BQ16-1

Frequencies

GnomAD3 genomes

AF:

0.000105

AC:

AN:

151996

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000590

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000211

AC:

AN:

250896

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135596

show subpopulations

Gnomad AFR exome

AF:

0.000246

Gnomad AMR exome

AF:

0.000261

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000294

Gnomad FIN exome

AF:

0.000555

Gnomad NFE exome

AF:

0.000124

Gnomad OTH exome

AF:

0.000654

GnomAD4 exome

AF:

0.0000753

AC:

110

AN:

1460658

Hom.:

Cov.:

AF XY:

0.0000839

AC XY:

AN XY:

726698

show subpopulations

Gnomad4 AFR exome

AF:

0.000120

Gnomad4 AMR exome

AF:

0.000672

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000253

Gnomad4 SAS exome

AF:

0.000162

Gnomad4 FIN exome

AF:

0.000468

Gnomad4 NFE exome

AF:

0.0000270

Gnomad4 OTH exome

AF:

0.0000994

GnomAD4 genome

AF:

0.000105

AC:

AN:

152112

Hom.:

Cov.:

AF XY:

0.000135

AC XY:

AN XY:

74324

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000240

Hom.:

Bravo

AF:

0.0000907

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.000247

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.980G>A (p.R327Q) alteration is located in exon 10 (coding exon 9) of the SPOCK3 gene. This alteration results from a G to A substitution at nucleotide position 980, causing the arginine (R) at amino acid position 327 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_addAF

Benign

-0.42

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Benign

0.52

DEOGEN2

Benign

0.0066

.;T;.;.;.;T;T;.;.;T;.;.

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.40

FATHMM_MKL

Benign

0.52

LIST_S2

Uncertain

0.89

D;.;D;.;.;.;.;D;D;D;D;D

M_CAP

Benign

0.015

MetaRNN

Benign

0.023

T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.3

.;N;.;.;.;N;N;.;.;N;.;.

MutationTaster

Benign

0.93

D;D;D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Benign

0.26

PROVEAN

Benign

0.20

N;N;N;N;N;N;N;.;N;N;N;N

REVEL

Benign

0.10

Sift

Benign

0.64

T;T;T;T;T;T;T;.;T;T;T;T

Sift4G

Benign

0.58

T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

0.064, 0.024

.;B;.;B;B;B;B;.;.;B;.;B

Vest4

0.098

MVP

0.69

MPC

0.20

ClinPred

0.018

GERP RS

3.1

Varity_R

0.031

gMVP

0.26

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over