7-99052279-T-A
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_181349.3(SMURF1):c.647A>T(p.Asp216Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000205 in 1,611,754 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000096 ( 0 hom. )
Consequence
SMURF1
NM_181349.3 missense
NM_181349.3 missense
Scores
1
17
Clinical Significance
Conservation
PhyloP100: 5.96
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 -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.07582313).
BS2
High AC in GnomAd4 at 19 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SMURF1 | NM_181349.3 | c.647A>T | p.Asp216Val | missense_variant | 7/18 | ENST00000361368.7 | NP_851994.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SMURF1 | ENST00000361368.7 | c.647A>T | p.Asp216Val | missense_variant | 7/18 | 1 | NM_181349.3 | ENSP00000355326 | P1 | |
SMURF1 | ENST00000361125.1 | c.647A>T | p.Asp216Val | missense_variant | 7/19 | 1 | ENSP00000354621 | |||
SMURF1 | ENST00000480055.5 | n.945A>T | non_coding_transcript_exon_variant | 7/7 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000125 AC: 19AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000400 AC: 10AN: 249902Hom.: 0 AF XY: 0.0000370 AC XY: 5AN XY: 134984
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GnomAD4 exome AF: 0.00000959 AC: 14AN: 1459568Hom.: 0 Cov.: 37 AF XY: 0.0000110 AC XY: 8AN XY: 725812
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GnomAD4 genome AF: 0.000125 AC: 19AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74356
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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 | Dec 28, 2022 | The c.647A>T (p.D216V) alteration is located in exon 7 (coding exon 7) of the SMURF1 gene. This alteration results from a A to T substitution at nucleotide position 647, causing the aspartic acid (D) at amino acid position 216 to be replaced by a valine (V). 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
DEOGEN2
Benign
.;T
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
Benign
T
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
B;B
Vest4
MVP
MPC
0.50
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