Variant 4-166792232-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001040159.2(SPOCK3):c.647C>A(p.Ala216Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00000744 in 1,613,640 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000068 ( 0 hom. )

Consequence

SPOCK3
NM_001040159.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.56

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOCK3	NM_001040159.2 linkuse as main transcript	c.647C>A	p.Ala216Asp	missense_variant	7/11	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.647C>A	p.Ala216Asp	missense_variant	7/11	1	NM_001040159.2	ENSP00000350153	A2	Q9BQ16-1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152042

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251322

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135824

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000684

AC:

AN:

1461598

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727098

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:

0.00000899

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152042

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74240

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:

0.0000294

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000189

ExAC

AF:

0.00000824

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

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

Jan 24, 2024

The c.656C>A (p.A219D) alteration is located in exon 8 (coding exon 7) of the SPOCK3 gene. This alteration results from a C to A substitution at nucleotide position 656, causing the alanine (A) at amino acid position 219 to be replaced by an aspartic acid (D). 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

Uncertain

0.42

BayesDel_addAF

Pathogenic

0.37

BayesDel_noAF

Pathogenic

0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.15

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

Eigen

Benign

0.0053

Eigen_PC

Benign

0.18

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.93

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

M_CAP

Benign

0.071

MetaRNN

Uncertain

0.48

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

MetaSVM

Benign

-0.30

MutationAssessor

Benign

1.5

.;L;.;.;.;L;L;.;L;.;.;.;.

MutationTaster

Benign

1.0

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

PrimateAI

Uncertain

0.67

PROVEAN

Uncertain

-3.5

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

REVEL

Benign

0.28

Sift

Uncertain

0.013

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

Sift4G

Uncertain

0.035

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

Polyphen

0.54, 0.49

.;P;.;P;P;P;P;.;P;.;P;.;.

Vest4

0.84

MutPred

0.47

.;Loss of MoRF binding (P = 0.0502);.;.;.;Loss of MoRF binding (P = 0.0502);Loss of MoRF binding (P = 0.0502);.;Loss of MoRF binding (P = 0.0502);.;.;.;.;

MVP

0.84

MPC

0.39

ClinPred

0.95

GERP RS

5.3

Varity_R

0.72

gMVP

0.71

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