Variant chr14-70010791-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

SMOC1 (HGNC:):

SMOC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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/exons	MANE	Protein	UniProt
SMOC1	NM_001034852.3 linkuse as main transcript	c.702C>T	p.Ala234Ala	synonymous_variant	8/12	ENST00000361956.8	NP_001030024.1	Q9H4F8-2
SMOC1	NM_022137.6 linkuse as main transcript	c.702C>T	p.Ala234Ala	synonymous_variant	8/12		NP_071420.1	Q9H4F8-1A0A024R6E0
SMOC1	XM_005267995.2 linkuse as main transcript	c.735C>T	p.Ala245Ala	synonymous_variant	8/12
SMOC1	XM_005267996.2 linkuse as main transcript	c.735C>T	p.Ala245Ala	synonymous_variant	8/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMOC1	ENST00000361956.8 linkuse as main transcript	c.702C>T	p.Ala234Ala	synonymous_variant	8/12	1	NM_001034852.3	ENSP00000355110.4	Q9H4F8-2
SMOC1	ENST00000381280.4 linkuse as main transcript	c.702C>T	p.Ala234Ala	synonymous_variant	8/12	1		ENSP00000370680.4	Q9H4F8-1
SMOC1	ENST00000557483.1 linkuse as main transcript	n.280C>T		non_coding_transcript_exon_variant	2/3	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

GnomAD3 exomes

AF:

0.211

AC:

53137

AN:

251426

Hom.:

6791

AF XY:

0.208

AC XY:

28290

AN XY:

135892

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 SAS exome

AF:

0.201

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

Gnomad4 AFR exome

AF:

0.0339

Gnomad4 AMR exome

AF:

0.337

Gnomad4 ASJ exome

AF:

0.148

Gnomad4 EAS exome

AF:

0.409

Gnomad4 SAS exome

AF:

0.202

Gnomad4 FIN exome

AF:

0.169

Gnomad4 NFE exome

AF:

0.187

Gnomad4 OTH exome

AF:

0.191

GnomAD4 genome

AF:

0.159

AC:

24249

AN:

152218

Hom.:

2684

Cov.:

AF XY:

0.165

AC XY:

12262

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.0408

Gnomad4 AMR

AF:

0.272

Gnomad4 ASJ

AF:

0.145

Gnomad4 EAS

AF:

0.404

Gnomad4 SAS

AF:

0.210

Gnomad4 FIN

AF:

0.186

Gnomad4 NFE

AF:

0.181

Gnomad4 OTH

AF:

0.172

Alfa

AF:

0.175

Hom.:

5910

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 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

-0.38

CADD

Benign

DANN

Benign

0.67

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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