Variant 14-69879761-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001034852.3(SMOC1):c.83G>T(p.Arg28Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000126 in 1,590,974 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

SMOC1
NM_001034852.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.92

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19303316).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMOC1	NM_001034852.3 linkuse as main transcript	c.83G>T	p.Arg28Leu	missense_variant	1/12	ENST00000361956.8	NP_001030024.1	Q9H4F8-2
SMOC1	NM_022137.6 linkuse as main transcript	c.83G>T	p.Arg28Leu	missense_variant	1/12		NP_071420.1	Q9H4F8-1A0A024R6E0
SMOC1	XM_005267995.2 linkuse as main transcript	c.83G>T	p.Arg28Leu	missense_variant	1/12
SMOC1	XM_005267996.2 linkuse as main transcript	c.83G>T	p.Arg28Leu	missense_variant	1/12

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMOC1	ENST00000361956.8 linkuse as main transcript	c.83G>T	p.Arg28Leu	missense_variant	1/12	1	NM_001034852.3	ENSP00000355110.4	Q9H4F8-2
SMOC1	ENST00000381280.4 linkuse as main transcript	c.83G>T	p.Arg28Leu	missense_variant	1/12	1		ENSP00000370680.4	Q9H4F8-1
SMOC1	ENST00000555917.1 linkuse as main transcript	n.404+15547G>T		intron_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152120

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD4 exome

AF:

0.0000111

AC:

AN:

1438854

Hom.:

Cov.:

AF XY:

0.00000978

AC XY:

AN XY:

715592

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000689

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000119

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000271

Gnomad4 OTH exome

AF:

0.000150

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152120

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74310

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000478

Bravo

AF:

0.0000416

ExAC

AF:

0.0000166

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Inborn genetic diseases

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 12, 2024

The c.83G>T (p.R28L) alteration is located in exon 1 (coding exon 1) of the SMOC1 gene. This alteration results from a G to T substitution at nucleotide position 83, causing the arginine (R) at amino acid position 28 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.029

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.11

.;T

Eigen

Benign

-0.13

Eigen_PC

Benign

0.026

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.77

T;T

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.19

T;T

MetaSVM

Benign

-0.89

MutationAssessor

Benign

0.34

N;N

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-1.7

N;N

REVEL

Benign

0.17

Sift

Benign

0.18

T;T

Sift4G

Benign

0.11

T;T

Polyphen

0.28

B;B

Vest4

0.43

MutPred

0.41

Gain of sheet (P = 0.0125);Gain of sheet (P = 0.0125);

MVP

0.58

MPC

0.41

ClinPred

0.50

GERP RS

5.0

Varity_R

0.27

gMVP

0.28

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