Genetic Variant SMOC1:p.Gln42Gln (chr14-69952164-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_001034852.3(SMOC1):c.126G>A(p.Gln42Gln) 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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.04

Publications

19 publications found

Variant links:

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]

SMOC1 Gene-Disease associations (from GenCC):

microphthalmia with limb anomalies
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

SMOC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001034852.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SMOC1	NM_001034852.3	MANE Select	c.126G>A	p.Gln42Gln	synonymous	Exon 2 of 12	NP_001030024.1
SMOC1	NM_001425244.1		c.126G>A	p.Gln42Gln	synonymous	Exon 2 of 12	NP_001412173.1
SMOC1	NM_001425245.1		c.126G>A	p.Gln42Gln	synonymous	Exon 2 of 12	NP_001412174.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
SMOC1	ENST00000361956.8	TSL:1 MANE Select	c.126G>A	p.Gln42Gln	synonymous	Exon 2 of 12	ENSP00000355110.4
SMOC1	ENST00000381280.4	TSL:1	c.126G>A	p.Gln42Gln	synonymous	Exon 2 of 12	ENSP00000370680.4
SMOC1	ENST00000553839.1	TSL:5	n.28G>A		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31853

AN:

152004

Hom.:

4242

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.261

AC:

65722

AN:

251400

AF XY:

0.258

show subpopulations

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 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.:

AF XY:

0.256

AC XY:

186424

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.0426

AC:

1425

AN:

33480

American (AMR)

AF:

0.373

AC:

16681

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

6415

AN:

26134

East Asian (EAS)

AF:

0.384

AC:

15247

AN:

39698

South Asian (SAS)

AF:

0.207

AC:

17843

AN:

86258

European-Finnish (FIN)

AF:

0.268

AC:

14313

AN:

53420

Middle Eastern (MID)

AF:

0.153

AC:

884

AN:

5768

European-Non Finnish (NFE)

AF:

0.259

AC:

288036

AN:

1111906

Other (OTH)

AF:

0.254

AC:

15335

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

16467

32934

49401

65868

82335

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

9772

19544

29316

39088

48860

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.209

AC:

31860

AN:

152122

Hom.:

4249

Cov.:

AF XY:

0.213

AC XY:

15841

AN XY:

74374

show subpopulations

African (AFR)

AF:

0.0524

AC:

2176

AN:

41508

American (AMR)

AF:

0.312

AC:

4773

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.239

AC:

830

AN:

3470

East Asian (EAS)

AF:

0.383

AC:

1980

AN:

5166

South Asian (SAS)

AF:

0.207

AC:

999

AN:

4820

European-Finnish (FIN)

AF:

0.284

AC:

3009

AN:

10580

Middle Eastern (MID)

AF:

0.120

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.256

AC:

17380

AN:

67978

Other (OTH)

AF:

0.217

AC:

458

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1211

2422

3633

4844

6055

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

340

680

1020

1360

1700

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.229

Hom.:

7007

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Microphthalmia with limb anomalies

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

7.4

(source)

DANN

Benign

0.73

PhyloP100

1.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over