rs3742909

chr14-69952164-G-Achr14-69952164-G-C

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001034852.3(SMOC1):c.126G>A(p.Gln42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 1,613,900 control chromosomes in the GnomAD database, including 54,615 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.21 (4249 hom., cov: 32)
  • Exomes 𝑓: 0.26 (50366 hom.)
• Consequence: SMOC1 NM_001034852.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.04

Genes affected

SMOC1 (HGNC:20318): (SPARC related modular calcium binding 1) This gene encodes a multi-domain secreted protein that may have a critical role in ocular and limb development. Mutations in this gene are associated with microphthalmia and limb anomalies. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BP6: Variant 14-69952164-G-A is Benign according to our data. Variant chr14-69952164-G-A is described in ClinVar as [Benign]. Clinvar id is 257188.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.04 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMOC1	NM_001034852.3	c.126G>A	p.Gln42=	synonymous_variant	2/12	ENST00000361956.8
SMOC1	NM_022137.6	c.126G>A	p.Gln42=	synonymous_variant	2/12
SMOC1	XM_005267995.2	c.126G>A	p.Gln42=	synonymous_variant	2/12
SMOC1	XM_005267996.2	c.126G>A	p.Gln42=	synonymous_variant	2/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMOC1	ENST00000361956.8	c.126G>A	p.Gln42=	synonymous_variant	2/12	1	NM_001034852.3	A2
SMOC1	ENST00000381280.4	c.126G>A	p.Gln42=	synonymous_variant	2/12	1		P4
SMOC1	ENST00000553839.1	n.28G>A		non_coding_transcript_exon_variant	1/4	5
SMOC1	ENST00000555917.1	n.431G>A		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31853 AN: 152004 Hom.: 4242 Cov.: 32

Gnomad AFR AF: 0.0526

Gnomad AMI AF: 0.241

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.239

Gnomad EAS AF: 0.383

Gnomad SAS AF: 0.207

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.256

Gnomad OTH AF: 0.219

GnomAD3 exomes AF: 0.261 AC: 65722 AN: 251400 Hom.: 9501 AF XY: 0.258 AC XY: 35067 AN XY: 135862

Gnomad AFR exome AF: 0.0492

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.244

Gnomad EAS exome AF: 0.388

Gnomad SAS exome AF: 0.202

Gnomad FIN exome AF: 0.273

Gnomad NFE exome AF: 0.252

Gnomad OTH exome AF: 0.248

GnomAD4 exome AF: 0.257 AC: 376179 AN: 1461778 Hom.: 50366 Cov.: 37 AF XY: 0.256 AC XY: 186424 AN XY: 727186

Gnomad4 AFR exome AF: 0.0426

Gnomad4 AMR exome AF: 0.373

Gnomad4 ASJ exome AF: 0.245

Gnomad4 EAS exome AF: 0.384

Gnomad4 SAS exome AF: 0.207

Gnomad4 FIN exome AF: 0.268

Gnomad4 NFE exome AF: 0.259

Gnomad4 OTH exome AF: 0.254

GnomAD4 genome AF: 0.209 AC: 31860 AN: 152122 Hom.: 4249 Cov.: 32 AF XY: 0.213 AC XY: 15841 AN XY: 74374

Gnomad4 AFR AF: 0.0524

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.239

Gnomad4 EAS AF: 0.383

Gnomad4 SAS AF: 0.207

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.256

Gnomad4 OTH AF: 0.217

Alfa AF: 0.232 Hom.: 5669

Bravo AF: 0.207

Asia WGS AF: 0.258 AC: 895 AN: 3478

EpiCase AF: 0.244

EpiControl AF: 0.243

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

-

- -

Microphthalmia with limb anomalies Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	7.4
Dann	Benign	0.73
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs3742909; hg19: chr14-70418881; COSMIC: COSV62759844;