Variant chr14-69952164-G-A 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.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

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.04

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Protein
SMOC1	NM_001034852.3 linkuse as main transcript	c.126G>A	p.Gln42=	synonymous_variant	2/12	ENST00000361956.8	NP_001030024.1
SMOC1	NM_022137.6 linkuse as main transcript	c.126G>A	p.Gln42=	synonymous_variant	2/12		NP_071420.1
SMOC1	XM_005267995.2 linkuse as main transcript	c.126G>A	p.Gln42=	synonymous_variant	2/12		XP_005268052.1
SMOC1	XM_005267996.2 linkuse as main transcript	c.126G>A	p.Gln42=	synonymous_variant	2/12		XP_005268053.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMOC1	ENST00000361956.8 linkuse as main transcript	c.126G>A	p.Gln42=	synonymous_variant	2/12	1	NM_001034852.3	ENSP00000355110	A2	Q9H4F8-2
SMOC1	ENST00000381280.4 linkuse as main transcript	c.126G>A	p.Gln42=	synonymous_variant	2/12	1		ENSP00000370680	P4	Q9H4F8-1
SMOC1	ENST00000553839.1 linkuse as main transcript	n.28G>A		non_coding_transcript_exon_variant	1/4	5
SMOC1	ENST00000555917.1 linkuse as main transcript	n.431G>A		non_coding_transcript_exon_variant	4/4	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

GnomAD3 exomes

AF:

0.261

AC:

65722

AN:

251400

Hom.:

9501

AF XY:

0.258

AC XY:

35067

AN XY:

135862

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 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.:

AF XY:

0.256

AC XY:

186424

AN XY:

727186

show subpopulations

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.:

AF XY:

0.213

AC XY:

15841

AN XY:

74374

show subpopulations

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:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

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