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rs112783338

Positions:

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting

The NM_005631.5(SMO):​c.2227C>A​(p.Pro743Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000126 in 1,614,188 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

Frequency

Genomes: 𝑓 0.00046 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000092 ( 1 hom. )

Consequence

SMO
NM_005631.5 missense

Scores

2
17

Clinical Significance

not provided no classification provided O:1

Conservation

PhyloP100: 0.0390
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (MetaRNN=0.0079242885).
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000459 (70/152368) while in subpopulation AFR AF= 0.00156 (65/41590). AF 95% confidence interval is 0.00126. There are 0 homozygotes in gnomad4. There are 42 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SMONM_005631.5 linkuse as main transcriptc.2227C>A p.Pro743Thr missense_variant 12/12 ENST00000249373.8
SMOXM_047420759.1 linkuse as main transcriptc.1837C>A p.Pro613Thr missense_variant 13/13

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SMOENST00000249373.8 linkuse as main transcriptc.2227C>A p.Pro743Thr missense_variant 12/121 NM_005631.5 P1
ENST00000466717.1 linkuse as main transcriptn.129+1103G>T intron_variant, non_coding_transcript_variant 3
SMOENST00000655644.1 linkuse as main transcriptc.*1982C>A 3_prime_UTR_variant, NMD_transcript_variant 12/12

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000433
AC:
66
AN:
152250
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00147
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000175
AC:
44
AN:
250950
Hom.:
0
AF XY:
0.000162
AC XY:
22
AN XY:
135802
show subpopulations
Gnomad AFR exome
AF:
0.00148
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000490
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000176
Gnomad OTH exome
AF:
0.000326
GnomAD4 exome
AF:
0.0000917
AC:
134
AN:
1461820
Hom.:
1
Cov.:
32
AF XY:
0.0000880
AC XY:
64
AN XY:
727210
show subpopulations
Gnomad4 AFR exome
AF:
0.00206
Gnomad4 AMR exome
AF:
0.0000447
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.000383
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000450
Gnomad4 OTH exome
AF:
0.000364
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000459
AC:
70
AN:
152368
Hom.:
0
Cov.:
32
AF XY:
0.000564
AC XY:
42
AN XY:
74514
show subpopulations
Gnomad4 AFR
AF:
0.00156
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000553
Hom.:
0
Bravo
AF:
0.000597
ESP6500AA
AF:
0.00204
AC:
9
ESP6500EA
AF:
0.00
AC:
0
ExAC
?
    Exome Aggregation Consortium database
AF:
0.000231
AC:
28
Asia WGS
AF:
0.00202
AC:
7
AN:
3478
EpiCase
AF:
0.00
EpiControl
AF:
0.000119

ClinVar

Significance: not provided
Submissions summary: Other:1
Revision: no classification provided
LINK: link

Submissions by phenotype

not specified Other:1
not provided, no classification providedreference populationITMISep 19, 2013- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.070
BayesDel_addAF
Benign
-0.42
T
BayesDel_noAF
Benign
-0.41
CADD
Benign
9.1
DANN
Benign
0.97
DEOGEN2
Benign
0.41
T
Eigen
Benign
-0.81
Eigen_PC
Benign
-0.81
FATHMM_MKL
Benign
0.10
N
LIST_S2
Benign
0.61
T
M_CAP
Benign
0.065
D
MetaRNN
Benign
0.0079
T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
0.34
N
MutationTaster
Benign
1.0
N
PrimateAI
Benign
0.42
T
PROVEAN
Benign
0.57
N
REVEL
Benign
0.11
Sift
Uncertain
0.027
D
Sift4G
Uncertain
0.037
D
Polyphen
0.0020
B
Vest4
0.14
MVP
0.55
MPC
0.098
ClinPred
0.011
T
GERP RS
0.088
Varity_R
0.054
gMVP
0.24

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.

Other links and lift over

dbSNP: rs112783338; hg19: chr7-128852155; API