6-168441433-T-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001166412.2(SMOC2):c.63T>G(p.Ala21=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 1,507,100 control chromosomes in the GnomAD database, including 36,751 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.29 (8327 hom., cov: 33)
  • Exomes 𝑓: 0.18 (28424 hom.)
• Consequence: SMOC2 NM_001166412.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.212

Genes affected

SMOC2 (HGNC:20323): (SPARC related modular calcium binding 2) This gene encodes a member of the SPARC family (secreted protein acidic and rich in cysteine/osteonectin/BM-40), which are highly expressed during embryogenesis and wound healing. The gene product is a matricellular protein which promotes matrix assembly and can stimulate endothelial cell proliferation and migration, as well as angiogenic activity. Associated with pulmonary function, this secretory gene product contains a Kazal domain, two thymoglobulin type-1 domains, and two EF-hand calcium-binding domains. The encoded protein may serve as a target for controlling angiogenesis in tumor growth and myocardial ischemia. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 6-168441433-T-G is Benign according to our data. Variant chr6-168441433-T-G is described in ClinVar as [Benign]. Clinvar id is 1257770.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.212 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMOC2	NM_001166412.2	c.63T>G	p.Ala21=	synonymous_variant	1/13	ENST00000356284.7
SMOC2	NM_022138.3	c.63T>G	p.Ala21=	synonymous_variant	1/13
SMOC2	XM_011536065.2	c.63T>G	p.Ala21=	synonymous_variant	1/13
SMOC2	XM_011536066.2	c.63T>G	p.Ala21=	synonymous_variant	1/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC2	ENST00000356284.7	c.63T>G	p.Ala21=	synonymous_variant	1/13	1	NM_001166412.2	P3
SMOC2	ENST00000354536.9	c.63T>G	p.Ala21=	synonymous_variant	1/13	1		A1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44154 AN: 151866 Hom.: 8315 Cov.: 33

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.454

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.239

Gnomad NFE AF: 0.162

Gnomad OTH AF: 0.253

GnomAD3 exomes AF: 0.242 AC: 25101 AN: 103790 Hom.: 3873 AF XY: 0.242 AC XY: 13956 AN XY: 57600

Gnomad AFR exome AF: 0.469

Gnomad AMR exome AF: 0.346

Gnomad ASJ exome AF: 0.181

Gnomad EAS exome AF: 0.398

Gnomad SAS exome AF: 0.360

Gnomad FIN exome AF: 0.121

Gnomad NFE exome AF: 0.144

Gnomad OTH exome AF: 0.213

GnomAD4 exome AF: 0.183 AC: 248438 AN: 1355128 Hom.: 28424 Cov.: 32 AF XY: 0.187 AC XY: 125250 AN XY: 668024

Gnomad4 AFR exome AF: 0.532

Gnomad4 AMR exome AF: 0.330

Gnomad4 ASJ exome AF: 0.191

Gnomad4 EAS exome AF: 0.433

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.132

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.210

GnomAD4 genome AF: 0.291 AC: 44193 AN: 151972 Hom.: 8327 Cov.: 33 AF XY: 0.293 AC XY: 21756 AN XY: 74258

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.454

Gnomad4 SAS AF: 0.374

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.162

Gnomad4 OTH AF: 0.254

Alfa AF: 0.196 Hom.: 1051

Bravo AF: 0.310

Asia WGS AF: 0.456 AC: 1578 AN: 3458

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
Cadd	Benign	12
Dann	Benign	0.64

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: rs73270928; hg19: chr6-168842113; COSMIC: COSV62439696;