4-167000408-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001040159.2(SPOCK3):c.291A>G(p.Val97=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00324 in 1,609,302 control chromosomes in the GnomAD database, including 159 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (93 hom., cov: 33)
  • Exomes 𝑓: 0.0018 (66 hom.)
• Consequence: SPOCK3 NM_001040159.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.05

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]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 4-167000408-T-C is Benign according to our data. Variant chr4-167000408-T-C is described in ClinVar as [Benign]. Clinvar id is 778163.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.05 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0585 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SPOCK3	NM_001040159.2	c.291A>G	p.Val97=	synonymous_variant	4/11	ENST00000357545.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SPOCK3	ENST00000357545.9	c.291A>G	p.Val97=	synonymous_variant	4/11	1	NM_001040159.2	A2

Frequencies

GnomAD3 genomes AF: 0.0172 AC: 2625 AN: 152176 Hom.: 92 Cov.: 33

Gnomad AFR AF: 0.0603

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00531

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000827

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00318

Gnomad NFE AF: 0.000279

Gnomad OTH AF: 0.00908

GnomAD3 exomes AF: 0.00444 AC: 1097 AN: 247294 Hom.: 31 AF XY: 0.00330 AC XY: 442 AN XY: 133746

Gnomad AFR exome AF: 0.0607

Gnomad AMR exome AF: 0.00254

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000134

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000187

Gnomad OTH exome AF: 0.00234

GnomAD4 exome AF: 0.00177 AC: 2576 AN: 1457008 Hom.: 66 Cov.: 27 AF XY: 0.00157 AC XY: 1135 AN XY: 724890

Gnomad4 AFR exome AF: 0.0606

Gnomad4 AMR exome AF: 0.00249

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000164

Gnomad4 FIN exome AF: 0.0000188

Gnomad4 NFE exome AF: 0.000134

Gnomad4 OTH exome AF: 0.00442

GnomAD4 genome AF: 0.0173 AC: 2636 AN: 152294 Hom.: 93 Cov.: 33 AF XY: 0.0174 AC XY: 1297 AN XY: 74456

Gnomad4 AFR AF: 0.0605

Gnomad4 AMR AF: 0.00530

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000279

Gnomad4 OTH AF: 0.00899

Alfa AF: 0.00801 Hom.: 16

Bravo AF: 0.0194

Asia WGS AF: 0.00433 AC: 15 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Mar 30, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.8
Dann	Benign	0.60

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

Other links and lift over

dbSNP: rs35168179; hg19: chr4-167921559;