Variant 4-166735025-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001040159.2(SPOCK3):c.1198G>A(p.Asp400Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000253 in 1,583,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

SPOCK3
NM_001040159.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.88

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.16796559).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOCK3	NM_001040159.2 linkuse as main transcript	c.1198G>A	p.Asp400Asn	missense_variant	11/11	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.1198G>A	p.Asp400Asn	missense_variant	11/11	1	NM_001040159.2	ENSP00000350153	A2	Q9BQ16-1

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151698

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000210

AC:

AN:

1431308

Hom.:

Cov.:

AF XY:

0.00000140

AC XY:

AN XY:

714084

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000276

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151698

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74074

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.00000378

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

Apr 20, 2024

The c.1207G>A (p.D403N) alteration is located in exon 12 (coding exon 11) of the SPOCK3 gene. This alteration results from a G to A substitution at nucleotide position 1207, causing the aspartic acid (D) at amino acid position 403 to be replaced by an asparagine (N). 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

0.086

BayesDel_addAF

Benign

-0.095

BayesDel_noAF

Benign

-0.37

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.017

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

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.27

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.89

D;.;D;.;.;.;.;D;T;D;D;D

M_CAP

Benign

0.040

MetaRNN

Benign

0.17

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

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.1

.;M;.;.;.;M;M;.;.;M;.;.

MutationTaster

Benign

0.94

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

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.4

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

REVEL

Benign

0.19

Sift

Uncertain

0.010

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

Sift4G

Benign

0.10

T;D;T;D;D;D;D;T;D;D;T;D

Polyphen

0.15, 0.24

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

Vest4

0.23

MutPred

0.17

.;Gain of glycosylation at T399 (P = 0.0414);.;.;.;Gain of glycosylation at T399 (P = 0.0414);Gain of glycosylation at T399 (P = 0.0414);.;.;Gain of glycosylation at T399 (P = 0.0414);.;.;

MVP

0.76

MPC

0.16

ClinPred

0.72

GERP RS

4.3

Varity_R

0.097

gMVP

0.33

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

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