rs116640950

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

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

The NM_005631.5(SMO):c.2093C>G(p.Pro698Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00289 in 1,557,256 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0016 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0030 ( 9 hom. )

Consequence

SMO
NM_005631.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: 1.11

Variant links:

Genes affected

SMO (HGNC:11119): (smoothened, frizzled class receptor) The protein encoded by this gene is a G protein-coupled receptor that interacts with the patched protein, a receptor for hedgehog proteins. The encoded protein tranduces signals to other proteins after activation by a hedgehog protein/patched protein complex. [provided by RefSeq, Jul 2010]

SMO links:

ENSG00000243230 (HGNC:):

ENSG00000243230 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=0.0074903667).

BP6

Variant 7-129212180-C-G is Benign according to our data. Variant chr7-129212180-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 135260.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00164 (250/152370) while in subpopulation NFE AF= 0.00294 (200/68028). AF 95% confidence interval is 0.00261. There are 1 homozygotes in gnomad4. There are 126 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 9 SM gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SMO	NM_005631.5 link	c.2093C>G	p.Pro698Arg	missense_variant	Exon 12 of 12	ENST00000249373.8	NP_005622.1	Q99835
SMO	XM_047420759.1 link	c.1703C>G	p.Pro568Arg	missense_variant	Exon 13 of 13		XP_047276715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SMO	ENST00000249373.8 link	c.2093C>G	p.Pro698Arg	missense_variant	Exon 12 of 12	1	NM_005631.5	ENSP00000249373.3		Q99835

Frequencies

GnomAD3 genomes

AF:

0.00164

AC:

250

AN:

152252

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000530

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00111

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00294

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.00172

AC:

280

AN:

162392

Hom.:

AF XY:

0.00172

AC XY:

149

AN XY:

86540

show subpopulations

Gnomad AFR exome

AF:

0.000115

Gnomad AMR exome

AF:

0.000912

Gnomad ASJ exome

AF:

0.000234

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00122

Gnomad FIN exome

AF:

0.000891

Gnomad NFE exome

AF:

0.00308

Gnomad OTH exome

AF:

0.00287

GnomAD4 exome

AF:

0.00303

AC:

4255

AN:

1404886

Hom.:

Cov.:

AF XY:

0.00295

AC XY:

2047

AN XY:

693738

show subpopulations

Gnomad4 AFR exome

AF:

0.000472

Gnomad4 AMR exome

AF:

0.000912

Gnomad4 ASJ exome

AF:

0.0000396

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000973

Gnomad4 FIN exome

AF:

0.000952

Gnomad4 NFE exome

AF:

0.00363

Gnomad4 OTH exome

AF:

0.00265

GnomAD4 genome

AF:

0.00164

AC:

250

AN:

152370

Hom.:

Cov.:

AF XY:

0.00169

AC XY:

126

AN XY:

74514

show subpopulations

Gnomad4 AFR

AF:

0.000529

Gnomad4 AMR

AF:

0.00111

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000621

Gnomad4 FIN

AF:

0.000565

Gnomad4 NFE

AF:

0.00294

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.00236

Hom.:

Bravo

AF:

0.00150

TwinsUK

AF:

0.00405

AC:

ALSPAC

AF:

0.00363

AC:

ESP6500AA

AF:

0.000698

AC:

ESP6500EA

AF:

0.00226

AC:

ExAC

AF:

0.00134

AC:

156

ClinVar

Significance: Likely benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:4

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Mar 01, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 24728327) -

Mar 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SMO: BP4, BS2 -

SMO-related disorder

Benign:1

Apr 25, 2022

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

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). -

not specified

Other:1

Sep 19, 2013

ITMI

Significance: not provided

Review Status: no classification provided

Collection Method: reference population

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.81

DEOGEN2

Benign

0.26

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.52

MetaRNN

Benign

0.0075

MetaSVM

Benign

-0.70

MutationAssessor

Benign

0.81

PrimateAI

Benign

0.42

PROVEAN

Benign

0.75

REVEL

Benign

0.15

Sift

Benign

0.31

Sift4G

Benign

0.82

Polyphen

0.0

Vest4

0.053

MVP

0.71

MPC

0.070

ClinPred

0.0073

GERP RS

4.5

Varity_R

0.045

gMVP

0.16

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