6-168441267-C-T

Variant names:

• chr6-168441267-C-T
• rs143067962
• NM_001166412.2:c.-104C>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0620
• Publications: 3 publications found

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 Gene-Disease associations (from GenCC):

• dentin dysplasia type I

  Inheritance: AR Classification: STRONG, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• atypical dentin dysplasia due to SMOC2 deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC2	NM_001166412.2	c.-104C>T		5_prime_UTR_variant	Exon 1 of 13	ENST00000356284.7	NP_001159884.1
SMOC2	NM_022138.3	c.-104C>T		5_prime_UTR_variant	Exon 1 of 13		NP_071421.1
SMOC2	XM_011536065.2	c.-104C>T		5_prime_UTR_variant	Exon 1 of 13		XP_011534367.1
SMOC2	XM_011536066.2	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	ENST00000356284.7	c.-104C>T		5_prime_UTR_variant	Exon 1 of 13	1	NM_001166412.2	ENSP00000348630.3
SMOC2	ENST00000354536.9	c.-104C>T		5_prime_UTR_variant	Exon 1 of 13	1		ENSP00000346537.5

Frequencies

GnomAD3 genomes AF: 0.0648 AC: 9856 AN: 152058 Hom.: 384 Cov.: 33

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.: 29 AF XY: 0.0843 AC XY: 50069 AN XY: 594226

African (AFR) AF: 0.0302 AC: 717 AN: 23778

American (AMR) AF: 0.0370 AC: 417 AN: 11266

Ashkenazi Jewish (ASJ) AF: 0.0606 AC: 1055 AN: 17416

East Asian (EAS) AF: 0.000560 AC: 15 AN: 26762

South Asian (SAS) AF: 0.0632 AC: 3386 AN: 53606

European-Finnish (FIN) AF: 0.0792 AC: 2387 AN: 30140

Middle Eastern (MID) AF: 0.0552 AC: 193 AN: 3494

European-Non Finnish (NFE) AF: 0.0916 AC: 92138 AN: 1006190

Other (OTH) AF: 0.0713 AC: 3587 AN: 50338

GnomAD4 genome AF: 0.0647 AC: 9851 AN: 152166 Hom.: 383 Cov.: 33 AF XY: 0.0631 AC XY: 4692 AN XY: 74388

African (AFR) AF: 0.0315 AC: 1308 AN: 41548

American (AMR) AF: 0.0425 AC: 649 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3470

East Asian (EAS) AF: 0.00272 AC: 14 AN: 5154

South Asian (SAS) AF: 0.0557 AC: 269 AN: 4830

European-Finnish (FIN) AF: 0.0746 AC: 791 AN: 10606

Middle Eastern (MID) AF: 0.0582 AC: 17 AN: 292

European-Non Finnish (NFE) AF: 0.0930 AC: 6317 AN: 67958

Other (OTH) AF: 0.0573 AC: 121 AN: 2112

Alfa AF: 0.0721 Hom.: 59

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

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
PhyloP100		-0.062
PromoterAI		-0.044	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs143067962; hg19: chr6-168841947;