rs61746143
Positions:
Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2
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
NM_005631.5 missense
Scores
1
9
8
Clinical Significance
Conservation
PhyloP100: 5.28
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 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_single_submitter, 1 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 | c.503G>A | p.Arg168His | missense_variant | 2/12 | ENST00000249373.8 | |
SMO | XM_047420759.1 | c.113G>A | p.Arg38His | missense_variant | 3/13 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMO | ENST00000249373.8 | c.503G>A | p.Arg168His | missense_variant | 2/12 | 1 | NM_005631.5 | P1 | |
SMO | ENST00000655644.1 | c.*367G>A | 3_prime_UTR_variant, NMD_transcript_variant | 3/12 |
Frequencies
GnomAD3 genomes ? AF: 0.00302 AC: 459AN: 152194Hom.: 9 Cov.: 32
GnomAD3 genomes
?
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32
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GnomAD3 exomes AF: 0.00731 AC: 1747AN: 239140Hom.: 36 AF XY: 0.00975 AC XY: 1270AN XY: 130206
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GnomAD4 exome AF: 0.00467 AC: 6784AN: 1451588Hom.: 125 Cov.: 32 AF XY: 0.00612 AC XY: 4420AN XY: 722256
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GnomAD4 genome ? AF: 0.00302 AC: 460AN: 152312Hom.: 9 Cov.: 32 AF XY: 0.00384 AC XY: 286AN XY: 74492
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ESP6500AA
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ExAC
?
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963
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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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
LIST_S2
Uncertain
D
MetaRNN
Benign
T
MetaSVM
Uncertain
T
MutationAssessor
Benign
L
MutationTaster
Benign
D
PrimateAI
Benign
T
PROVEAN
Uncertain
D
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
P
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at