chr7-99052427-C-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4
The NM_181349.3(SMURF1):c.499G>A(p.Gly167Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000177 in 1,584,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )
Consequence
SMURF1
NM_181349.3 missense
NM_181349.3 missense
Scores
2
15
Clinical Significance
Conservation
PhyloP100: 5.84
Genes affected
SMURF1 (HGNC:16807): (SMAD specific E3 ubiquitin protein ligase 1) This gene encodes a ubiquitin ligase that is specific for receptor-regulated SMAD proteins in the bone morphogenetic protein (BMP) pathway. This protein plays a key roll in the regulation of cell motility, cell signalling, and cell polarity. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Dec 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -1 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.37899938).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
SMURF1 | NM_181349.3 | c.499G>A | p.Gly167Arg | missense_variant | 7/18 | ENST00000361368.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
SMURF1 | ENST00000361368.7 | c.499G>A | p.Gly167Arg | missense_variant | 7/18 | 1 | NM_181349.3 | P1 | |
SMURF1 | ENST00000361125.1 | c.499G>A | p.Gly167Arg | missense_variant | 7/19 | 1 | |||
SMURF1 | ENST00000480055.5 | n.797G>A | non_coding_transcript_exon_variant | 7/7 | 3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32
GnomAD3 genomes
?
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GnomAD3 exomes AF: 0.0000130 AC: 3AN: 230948Hom.: 0 AF XY: 0.0000161 AC XY: 2AN XY: 124266
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GnomAD4 exome AF: 0.0000188 AC: 27AN: 1432382Hom.: 0 Cov.: 37 AF XY: 0.0000141 AC XY: 10AN XY: 709240
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152178Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74332
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 21, 2024 | The c.499G>A (p.G167R) alteration is located in exon 7 (coding exon 7) of the SMURF1 gene. This alteration results from a G to A substitution at nucleotide position 499, causing the glycine (G) at amino acid position 167 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MutPred
Loss of glycosylation at S166 (P = 0.0569);Loss of glycosylation at S166 (P = 0.0569);
MVP
MPC
0.40
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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