Variant 7-129203555-G-A details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_005631.5(SMO):c.503G>A(p.Arg168His) variant causes a missense change. The variant allele was found at a frequency of 0.00452 in 1,603,900 control chromosomes in the GnomAD database, including 134 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 9 hom., cov: 32)

Exomes 𝑓: 0.0047 ( 125 hom. )

Consequence

SMO
NM_005631.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1O:1

Conservation

PhyloP100: 5.28

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:

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=0.017337203).

BP6

Variant 7-129203555-G-A is Benign according to our data. Variant chr7-129203555-G-A is described in ClinVar as [Benign]. Clinvar id is 135266.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00302 (460/152312) while in subpopulation SAS AF= 0.0458 (221/4828). AF 95% confidence interval is 0.0408. There are 9 homozygotes in gnomad4. There are 286 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 9 SM gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMO	NM_005631.5 linkuse as main transcript	c.503G>A	p.Arg168His	missense_variant	2/12	ENST00000249373.8
SMO	XM_047420759.1 linkuse as main transcript	c.113G>A	p.Arg38His	missense_variant	3/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMO	ENST00000249373.8 linkuse as main transcript	c.503G>A	p.Arg168His	missense_variant	2/12	1	NM_005631.5	P1
SMO	ENST00000655644.1 linkuse as main transcript	c.*367G>A		3_prime_UTR_variant, NMD_transcript_variant	3/12

Frequencies

GnomAD3 genomes

AF:

0.00302

AC:

459

AN:

152194

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00229

Gnomad ASJ

AF:

0.00778

Gnomad EAS

AF:

0.000385

Gnomad SAS

AF:

0.0455

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00237

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00731

AC:

1747

AN:

239140

Hom.:

AF XY:

0.00975

AC XY:

1270

AN XY:

130206

show subpopulations

Gnomad AFR exome

AF:

0.000190

Gnomad AMR exome

AF:

0.00146

Gnomad ASJ exome

AF:

0.00613

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0445

Gnomad FIN exome

AF:

0.000410

Gnomad NFE exome

AF:

0.00243

Gnomad OTH exome

AF:

0.00384

GnomAD4 exome

AF:

0.00467

AC:

6784

AN:

1451588

Hom.:

125

Cov.:

AF XY:

0.00612

AC XY:

4420

AN XY:

722256

show subpopulations

Gnomad4 AFR exome

AF:

0.000478

Gnomad4 AMR exome

AF:

0.00170

Gnomad4 ASJ exome

AF:

0.00533

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0462

Gnomad4 FIN exome

AF:

0.000588

Gnomad4 NFE exome

AF:

0.00197

Gnomad4 OTH exome

AF:

0.00481

GnomAD4 genome

AF:

0.00302

AC:

460

AN:

152312

Hom.:

Cov.:

AF XY:

0.00384

AC XY:

286

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.00229

Gnomad4 ASJ

AF:

0.00778

Gnomad4 EAS

AF:

0.000386

Gnomad4 SAS

AF:

0.0458

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00237

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00250

Hom.:

Bravo

AF:

0.00186

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.00208

AC:

ESP6500AA

AF:

0.000454

AC:

ESP6500EA

AF:

0.00291

AC:

ExAC

AF:

0.00793

AC:

963

Asia WGS

AF:

0.0110

AC:

AN:

3478

EpiCase

AF:

0.00371

EpiControl

AF:

0.00368

ClinVar

Significance: Benign

Submissions summary: Benign:1Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Dec 31, 2019

- -

not specified

Other:1

not provided, no classification provided

reference population

ITMI

Sep 19, 2013

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.094

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.26

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.79

Eigen

Uncertain

0.43

Eigen_PC

Uncertain

0.49

FATHMM_MKL

Benign

0.66

LIST_S2

Uncertain

0.90

MetaRNN

Benign

0.017

MetaSVM

Uncertain

-0.23

MutationAssessor

Benign

1.6

MutationTaster

Benign

0.95

PrimateAI

Benign

0.46

PROVEAN

Uncertain

-3.1

REVEL

Uncertain

0.43

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.018

Polyphen

0.77

Vest4

0.36

MVP

0.86

MPC

1.7

ClinPred

0.052

GERP RS

4.4

Varity_R

0.26

gMVP

0.46

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