chr14-69952141-C-G

Position:

chr14-69952141-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001034852.3(SMOC1):c.103C>G(p.Leu35Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00201 in 1,614,174 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0015 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0021 ( 7 hom. )

Consequence

SMOC1
NM_001034852.3 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.19

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01919642).

BP6

Variant 14-69952141-C-G is Benign according to our data. Variant chr14-69952141-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 769863.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00145 (221/152312) while in subpopulation AMR AF= 0.00209 (32/15302). AF 95% confidence interval is 0.00178. There are 1 homozygotes in gnomad4. There are 100 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 7 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SMOC1	NM_001034852.3 linkuse as main transcript	c.103C>G	p.Leu35Val	missense_variant	2/12	ENST00000361956.8	NP_001030024.1
SMOC1	NM_022137.6 linkuse as main transcript	c.103C>G	p.Leu35Val	missense_variant	2/12		NP_071420.1
SMOC1	XM_005267995.2 linkuse as main transcript	c.103C>G	p.Leu35Val	missense_variant	2/12		XP_005268052.1
SMOC1	XM_005267996.2 linkuse as main transcript	c.103C>G	p.Leu35Val	missense_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.103C>G	p.Leu35Val	missense_variant	2/12	1	NM_001034852.3	ENSP00000355110	A2	Q9H4F8-2
SMOC1	ENST00000381280.4 linkuse as main transcript	c.103C>G	p.Leu35Val	missense_variant	2/12	1		ENSP00000370680	P4	Q9H4F8-1
SMOC1	ENST00000553839.1 linkuse as main transcript	n.5C>G		non_coding_transcript_exon_variant	1/4	5
SMOC1	ENST00000555917.1 linkuse as main transcript	n.408C>G		non_coding_transcript_exon_variant	4/4	4

Frequencies

GnomAD3 genomes

AF:

0.00145

AC:

221

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000338

Gnomad AMI

AF:

0.0296

Gnomad AMR

AF:

0.00209

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00111

AC:

280

AN:

251420

Hom.:

AF XY:

0.000979

AC XY:

133

AN XY:

135884

show subpopulations

Gnomad AFR exome

AF:

0.000308

Gnomad AMR exome

AF:

0.00191

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000693

Gnomad NFE exome

AF:

0.00151

Gnomad OTH exome

AF:

0.00359

GnomAD4 exome

AF:

0.00207

AC:

3025

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00193

AC XY:

1407

AN XY:

727238

show subpopulations

Gnomad4 AFR exome

AF:

0.000269

Gnomad4 AMR exome

AF:

0.00188

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00120

Gnomad4 NFE exome

AF:

0.00246

Gnomad4 OTH exome

AF:

0.00217

GnomAD4 genome

AF:

0.00145

AC:

221

AN:

152312

Hom.:

Cov.:

AF XY:

0.00134

AC XY:

100

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.000337

Gnomad4 AMR

AF:

0.00209

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000471

Gnomad4 NFE

AF:

0.00206

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00146

Hom.:

Bravo

AF:

0.00145

TwinsUK

AF:

0.00270

AC:

ALSPAC

AF:

0.00234

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00233

AC:

ExAC

AF:

0.00119

AC:

144

EpiCase

AF:

0.00125

EpiControl

AF:

0.00213

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 18, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Mar 01, 2023	SMOC1: BS2 -

SMOC1-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 05, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.56

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.29

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

.;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.45

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.013

MetaRNN

Benign

0.019

T;T

MetaSVM

Benign

-0.72

MutationAssessor

Benign

0.69

N;N

MutationTaster

Benign

0.98

D;D

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.85

N;N

REVEL

Benign

0.13

Sift

Benign

0.090

T;T

Sift4G

Uncertain

0.040

D;D

Polyphen

0.95

P;D

Vest4

0.66

MVP

0.73

MPC

0.32

ClinPred

0.014

GERP RS

4.5

Varity_R

0.15

gMVP

0.40

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