14-70010791-C-T

Variant names:

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.702C>T(p.Ala234Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.19 in 1,613,988 control chromosomes in the GnomAD database, including 32,293 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2684 hom., cov: 32)

Exomes 𝑓: 0.19 ( 29609 hom. )

Consequence

SMOC1
NM_001034852.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0660

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=-0.38).

BP6

Variant 14-70010791-C-T is Benign according to our data. Variant chr14-70010791-C-T is described in ClinVar as Benign. ClinVar VariationId is 257189.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.066 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.39 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMOC1	NM_001034852.3 link	c.702C>T	p.Ala234Ala	synonymous_variant	Exon 8 of 12	ENST00000361956.8	NP_001030024.1	Q9H4F8-2
SMOC1	NM_001425244.1 link	c.735C>T	p.Ala245Ala	synonymous_variant	Exon 8 of 12		NP_001412173.1
SMOC1	NM_001425245.1 link	c.735C>T	p.Ala245Ala	synonymous_variant	Exon 8 of 12		NP_001412174.1
SMOC1	NM_022137.6 link	c.702C>T	p.Ala234Ala	synonymous_variant	Exon 8 of 12		NP_071420.1	Q9H4F8-1A0A024R6E0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SMOC1	ENST00000361956.8 link	c.702C>T	p.Ala234Ala	synonymous_variant	Exon 8 of 12	1	NM_001034852.3	ENSP00000355110.4	Q9H4F8-2
SMOC1	ENST00000381280.4 link	c.702C>T	p.Ala234Ala	synonymous_variant	Exon 8 of 12	1		ENSP00000370680.4	Q9H4F8-1
SMOC1	ENST00000557483.1 link	n.280C>T		non_coding_transcript_exon_variant	Exon 2 of 3	5

Frequencies

GnomAD3 genomes

AF:

0.159

AC:

24239

AN:

152100

Hom.:

2677

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0409

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.272

Gnomad ASJ

AF:

0.145

Gnomad EAS

AF:

0.404

Gnomad SAS

AF:

0.210

Gnomad FIN

AF:

0.186

Gnomad MID

AF:

0.0987

Gnomad NFE

AF:

0.181

Gnomad OTH

AF:

0.173

GnomAD2 exomes

AF:

0.211

AC:

53137

AN:

251426

AF XY:

0.208

show subpopulations

Gnomad AFR exome

AF:

0.0391

Gnomad AMR exome

AF:

0.342

Gnomad ASJ exome

AF:

0.148

Gnomad EAS exome

AF:

0.412

Gnomad FIN exome

AF:

0.170

Gnomad NFE exome

AF:

0.181

Gnomad OTH exome

AF:

0.188

GnomAD4 exome

AF:

0.193

AC:

282601

AN:

1461770

Hom.:

29609

Cov.:

AF XY:

0.194

AC XY:

140832

AN XY:

727186

show subpopulations

African (AFR)

AF:

0.0339

AC:

1134

AN:

33480

American (AMR)

AF:

0.337

AC:

15075

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.148

AC:

3860

AN:

26136

East Asian (EAS)

AF:

0.409

AC:

16227

AN:

39700

South Asian (SAS)

AF:

0.202

AC:

17406

AN:

86258

European-Finnish (FIN)

AF:

0.169

AC:

9022

AN:

53410

Middle Eastern (MID)

AF:

0.108

AC:

623

AN:

5768

European-Non Finnish (NFE)

AF:

0.187

AC:

207741

AN:

1111904

Other (OTH)

AF:

0.191

AC:

11513

AN:

60390

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

13011

26023

39034

52046

65057

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7438

14876

22314

29752

37190

<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:

0.159

AC:

24249

AN:

152218

Hom.:

2684

Cov.:

AF XY:

0.165

AC XY:

12262

AN XY:

74434

show subpopulations

African (AFR)

AF:

0.0408

AC:

1697

AN:

41560

American (AMR)

AF:

0.272

AC:

4168

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.145

AC:

503

AN:

3472

East Asian (EAS)

AF:

0.404

AC:

2088

AN:

5166

South Asian (SAS)

AF:

0.210

AC:

1013

AN:

4820

European-Finnish (FIN)

AF:

0.186

AC:

1970

AN:

10604

Middle Eastern (MID)

AF:

0.0959

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.181

AC:

12298

AN:

67982

Other (OTH)

AF:

0.172

AC:

363

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1012

2025

3037

4050

5062

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

270

540

810

1080

1350

<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:

0.171

Hom.:

8559

Bravo

AF:

0.162

Asia WGS

AF:

0.254

AC:

880

AN:

3478

EpiCase

AF:

0.172

EpiControl

AF:

0.168

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

May 04, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.38

CADD

Benign

(source)

DANN

Benign

0.67

PhyloP100

-0.066

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)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over