7-99047752-C-T
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Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3
The NM_181349.3(SMURF1):c.1084G>A(p.Glu362Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000031 in 1,614,108 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000014 ( 0 hom. )
Consequence
SMURF1
NM_181349.3 missense
NM_181349.3 missense
Scores
5
8
5
Clinical Significance
Conservation
PhyloP100: 7.90
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 Uncertain_significance. Variant got 3 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PP3
MetaRNN computational evidence supports a deleterious effect, 0.792
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMURF1 | NM_181349.3 | c.1084G>A | p.Glu362Lys | missense_variant | 10/18 | ENST00000361368.7 | NP_851994.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMURF1 | ENST00000361368.7 | c.1084G>A | p.Glu362Lys | missense_variant | 10/18 | 1 | NM_181349.3 | ENSP00000355326.2 | ||
SMURF1 | ENST00000361125.1 | c.1162G>A | p.Glu388Lys | missense_variant | 11/19 | 1 | ENSP00000354621.1 | |||
TRRAP | ENST00000468960.3 | n.819C>T | non_coding_transcript_exon_variant | 5/5 | 4 | |||||
TRRAP | ENST00000482799.3 | n.902C>T | non_coding_transcript_exon_variant | 6/6 | 3 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152214Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251490Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135920
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GnomAD4 exome AF: 0.00000137 AC: 2AN: 1461894Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727248
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GnomAD4 genome AF: 0.0000197 AC: 3AN: 152214Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74368
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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 | Sep 14, 2022 | The c.1162G>A (p.E388K) alteration is located in exon 11 (coding exon 11) of the SMURF1 gene. This alteration results from a G to A substitution at nucleotide position 1162, causing the glutamic acid (E) at amino acid position 388 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
CADD
Pathogenic
DANN
Pathogenic
DEOGEN2
Uncertain
.;D
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
D
MetaRNN
Pathogenic
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;L
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D
REVEL
Uncertain
Sift
Uncertain
D;D
Sift4G
Benign
T;D
Polyphen
D;D
Vest4
MVP
MPC
1.0
ClinPred
D
GERP RS
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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