Genetic Variant SPOCK3:p.Ser384Ser (chr4-166735071-G-A) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_001040159.2(SPOCK3):c.1152C>T(p.Ser384Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,602,170 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00011 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00013 ( 0 hom. )

Consequence

SPOCK3
NM_001040159.2 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.207

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 was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 4-166735071-G-A is Benign according to our data. Variant chr4-166735071-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 758169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.207 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SPOCK3	NM_001040159.2 link	c.1152C>T	p.Ser384Ser	synonymous_variant	Exon 11 of 11	ENST00000357545.9	NP_001035249.1	Q9BQ16-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SPOCK3	ENST00000357545.9 link	c.1152C>T	p.Ser384Ser	synonymous_variant	Exon 11 of 11	1	NM_001040159.2	ENSP00000350153.4		Q9BQ16-1

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

151356

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000485

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000331

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.000481

GnomAD2 exomes

AF:

0.000156

AC:

AN:

243842

AF XY:

0.000166

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000270

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000229

Gnomad OTH exome

AF:

0.000677

GnomAD4 exome

AF:

0.000128

AC:

185

AN:

1450696

Hom.:

Cov.:

AF XY:

0.000130

AC XY:

AN XY:

721760

show subpopulations

African (AFR)

AF:

0.000212

AC:

AN:

33036

American (AMR)

AF:

0.000296

AC:

AN:

43884

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25976

East Asian (EAS)

AF:

0.00

AC:

AN:

39090

South Asian (SAS)

AF:

0.0000237

AC:

AN:

84440

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53342

Middle Eastern (MID)

AF:

0.00157

AC:

AN:

5734

European-Non Finnish (NFE)

AF:

0.000128

AC:

141

AN:

1105204

Other (OTH)

AF:

0.000217

AC:

AN:

59990

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.458

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000112

AC:

AN:

151474

Hom.:

Cov.:

AF XY:

0.0000811

AC XY:

AN XY:

73994

show subpopulations

African (AFR)

AF:

0.0000484

AC:

AN:

41360

American (AMR)

AF:

0.000330

AC:

AN:

15142

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5150

South Asian (SAS)

AF:

0.00

AC:

AN:

4780

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10488

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

67780

Other (OTH)

AF:

0.000476

AC:

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.545

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000115

Hom.:

Bravo

AF:

0.000110

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 16, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

8.3

(source)

DANN

Benign

0.64

PhyloP100

-0.21

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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4-166735071-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over