Variant 4-166734925-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001040159.2(SPOCK3):c.1298T>A(p.Ile433Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00198 in 1,534,848 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.011 ( 30 hom., cov: 32)

Exomes 𝑓: 0.00098 ( 17 hom. )

Consequence

SPOCK3
NM_001040159.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 6.65

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006558448).

BP6

Variant 4-166734925-A-T is Benign according to our data. Variant chr4-166734925-A-T is described in ClinVar as [Benign]. Clinvar id is 769638.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.011 (1678/152058) while in subpopulation AFR AF= 0.0387 (1608/41536). AF 95% confidence interval is 0.0371. There are 30 homozygotes in gnomad4. There are 782 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 30 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOCK3	NM_001040159.2 linkuse as main transcript	c.1298T>A	p.Ile433Asn	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.1298T>A	p.Ile433Asn	missense_variant	11/11	1	NM_001040159.2	ENSP00000350153	A2	Q9BQ16-1

Frequencies

GnomAD3 genomes

AF:

0.0110

AC:

1671

AN:

151940

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0387

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00342

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00623

GnomAD3 exomes

AF:

0.00278

AC:

654

AN:

235222

Hom.:

AF XY:

0.00193

AC XY:

247

AN XY:

127834

show subpopulations

Gnomad AFR exome

AF:

0.0401

Gnomad AMR exome

AF:

0.00117

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000358

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000930

Gnomad OTH exome

AF:

0.000531

GnomAD4 exome

AF:

0.000981

AC:

1357

AN:

1382790

Hom.:

Cov.:

AF XY:

0.000835

AC XY:

576

AN XY:

689578

show subpopulations

Gnomad4 AFR exome

AF:

0.0360

Gnomad4 AMR exome

AF:

0.00143

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000508

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000133

Gnomad4 OTH exome

AF:

0.00215

GnomAD4 genome

AF:

0.0110

AC:

1678

AN:

152058

Hom.:

Cov.:

AF XY:

0.0105

AC XY:

782

AN XY:

74344

show subpopulations

Gnomad4 AFR

AF:

0.0387

Gnomad4 AMR

AF:

0.00342

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00616

Alfa

AF:

0.00308

Hom.:

Bravo

AF:

0.0125

ESP6500AA

AF:

0.0390

AC:

172

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00365

AC:

443

Asia WGS

AF:

0.00260

AC:

AN:

3476

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 18, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Benign

0.56

DEOGEN2

Benign

0.050

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

Eigen

Uncertain

0.47

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.96

LIST_S2

Benign

0.85

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

MetaRNN

Benign

0.0066

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

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.5

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

MutationTaster

Benign

0.75

D;D;D;D;D;D;D;N;N;N;N;N;N;N

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-2.8

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

REVEL

Benign

0.23

Sift

Pathogenic

0.0

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

Sift4G

Pathogenic

0.0

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

Polyphen

0.99, 0.99

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

Vest4

0.57

MVP

0.69

MPC

0.29

ClinPred

0.11

GERP RS

5.1

Varity_R

0.61

gMVP

0.36

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