Genetic Variant SMOC2:c.-104C>T (chr6-168441267-C-T) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001166412.2(SMOC2):c.-104C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0827 in 1,375,156 control chromosomes in the GnomAD database, including 5,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.065 ( 383 hom., cov: 33)

Exomes 𝑓: 0.085 ( 4750 hom. )

Consequence

SMOC2
NM_001166412.2 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0620

Variant links:

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]

SMOC2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 6-168441267-C-T is Benign according to our data. Variant chr6-168441267-C-T is described in ClinVar as [Benign]. Clinvar id is 1273584.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
SMOC2	NM_001166412.2 link	c.-104C>T	5_prime_UTR_variant	Exon 1 of 13	ENST00000356284.7	NP_001159884.1	Q9H3U7-1
SMOC2	NM_022138.3 link	c.-104C>T	5_prime_UTR_variant	Exon 1 of 13		NP_071421.1	Q9H3U7-2
SMOC2	XM_011536065.2 link	c.-104C>T	5_prime_UTR_variant	Exon 1 of 13		XP_011534367.1
SMOC2	XM_011536066.2 link	c.-104C>T	5_prime_UTR_variant	Exon 1 of 13		XP_011534368.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMOC2	ENST00000356284 link	c.-104C>T		5_prime_UTR_variant	Exon 1 of 13	1	NM_001166412.2	ENSP00000348630.3		Q9H3U7-1
SMOC2	ENST00000354536 link	c.-104C>T		5_prime_UTR_variant	Exon 1 of 13	1		ENSP00000346537.5		Q9H3U7-2

Frequencies

GnomAD3 genomes

AF:

0.0648

AC:

9856

AN:

152058

Hom.:

384

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0315

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.0425

Gnomad ASJ

AF:

0.0599

Gnomad EAS

AF:

0.00271

Gnomad SAS

AF:

0.0561

Gnomad FIN

AF:

0.0746

Gnomad MID

AF:

0.0573

Gnomad NFE

AF:

0.0930

Gnomad OTH

AF:

0.0578

GnomAD4 exome

AF:

0.0850

AC:

103895

AN:

1222990

Hom.:

4750

Cov.:

AF XY:

0.0843

AC XY:

50069

AN XY:

594226

show subpopulations

Gnomad4 AFR exome

AF:

0.0302

Gnomad4 AMR exome

AF:

0.0370

Gnomad4 ASJ exome

AF:

0.0606

Gnomad4 EAS exome

AF:

0.000560

Gnomad4 SAS exome

AF:

0.0632

Gnomad4 FIN exome

AF:

0.0792

Gnomad4 NFE exome

AF:

0.0916

Gnomad4 OTH exome

AF:

0.0713

GnomAD4 genome

AF:

0.0647

AC:

9851

AN:

152166

Hom.:

383

Cov.:

AF XY:

0.0631

AC XY:

4692

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.0315

Gnomad4 AMR

AF:

0.0425

Gnomad4 ASJ

AF:

0.0599

Gnomad4 EAS

AF:

0.00272

Gnomad4 SAS

AF:

0.0557

Gnomad4 FIN

AF:

0.0746

Gnomad4 NFE

AF:

0.0930

Gnomad4 OTH

AF:

0.0573

Alfa

AF:

0.0740

Hom.:

Bravo

AF:

0.0597

Asia WGS

AF:

0.0420

AC:

145

AN:

3460

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jun 19, 2021

GeneDx

Significance: 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

-0.66

CADD

Benign

5.8

DANN

Benign

0.96

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

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