Variant 4-167000374-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001040159.2(SPOCK3):c.325A>G(p.Ile109Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00564 in 1,592,230 control chromosomes in the GnomAD database, including 469 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.030 ( 254 hom., cov: 33)

Exomes 𝑓: 0.0030 ( 215 hom. )

Consequence

SPOCK3
NM_001040159.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.307

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 Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0021817386).

BP6

Variant 4-167000374-T-C is Benign according to our data. Variant chr4-167000374-T-C is described in ClinVar as [Benign]. Clinvar id is 769639.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SPOCK3	NM_001040159.2 linkuse as main transcript	c.325A>G	p.Ile109Val	missense_variant	4/11	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.325A>G	p.Ile109Val	missense_variant	4/11	1	NM_001040159.2	ENSP00000350153	A2	Q9BQ16-1

Frequencies

GnomAD3 genomes

AF:

0.0305

AC:

4636

AN:

152152

Hom.:

253

Cov.:

show subpopulations

Gnomad AFR

AF:

0.105

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0132

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:

0.000265

Gnomad OTH

AF:

0.0224

GnomAD3 exomes

AF:

0.00787

AC:

1915

AN:

243418

Hom.:

AF XY:

0.00592

AC XY:

780

AN XY:

131712

show subpopulations

Gnomad AFR exome

AF:

0.110

Gnomad AMR exome

AF:

0.00415

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000112

Gnomad SAS exome

AF:

0.000104

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000197

Gnomad OTH exome

AF:

0.00274

GnomAD4 exome

AF:

0.00302

AC:

4342

AN:

1439960

Hom.:

215

Cov.:

AF XY:

0.00262

AC XY:

1878

AN XY:

717172

show subpopulations

Gnomad4 AFR exome

AF:

0.108

Gnomad4 AMR exome

AF:

0.00491

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000765

Gnomad4 SAS exome

AF:

0.000202

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000141

Gnomad4 OTH exome

AF:

0.00667

GnomAD4 genome

AF:

0.0305

AC:

4641

AN:

152270

Hom.:

254

Cov.:

AF XY:

0.0298

AC XY:

2215

AN XY:

74442

show subpopulations

Gnomad4 AFR

AF:

0.105

Gnomad4 AMR

AF:

0.0132

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.0222

Alfa

AF:

0.00922

Hom.:

108

Bravo

AF:

0.0354

ESP6500AA

AF:

0.0994

AC:

438

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.00978

AC:

1187

Asia WGS

AF:

0.00837

AC:

AN:

3478

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

0.069

BayesDel_addAF

Benign

-0.70

BayesDel_noAF

Benign

-0.68

CADD

Benign

2.0

DANN

Benign

0.51

DEOGEN2

Benign

0.0074

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

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.47

LIST_S2

Benign

0.74

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

MetaRNN

Benign

0.0022

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

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.81

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

MutationTaster

Benign

0.96

P;P;P;P;P;P;P;P;P;P;P;P;P;P;P

PrimateAI

Benign

0.30

PROVEAN

Benign

0.10

N;N;N;N;N;N;N;N;N;N;N;N;N;N

REVEL

Benign

0.052

Sift

Benign

0.86

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

Sift4G

Benign

0.76

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

Polyphen

0.0070

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

Vest4

0.056

MVP

0.15

MPC

0.14

ClinPred

0.0047

GERP RS

-3.7

Varity_R

0.033

gMVP

0.17

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