Variant 7-99052214-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_181349.3(SMURF1):c.712G>A(p.Glu238Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000142 in 1,410,412 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

SMURF1
NM_181349.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.69

Variant links:

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]

SMURF1 links:

SMURF1 (HGNC:):

SMURF1 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMURF1	NM_181349.3 linkuse as main transcript	c.712G>A	p.Glu238Lys	missense_variant	7/18	ENST00000361368.7	NP_851994.1	Q9HCE7-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SMURF1	ENST00000361368.7 linkuse as main transcript	c.712G>A	p.Glu238Lys	missense_variant	7/18	1	NM_181349.3	ENSP00000355326.2	Q9HCE7-2
SMURF1	ENST00000361125.1 linkuse as main transcript	c.712G>A	p.Glu238Lys	missense_variant	7/19	1		ENSP00000354621.1	Q9HCE7-1
SMURF1	ENST00000480055.5 linkuse as main transcript	n.1010G>A		splice_region_variant, non_coding_transcript_exon_variant	7/7	3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000449

AC:

AN:

222682

Hom.:

AF XY:

0.00000834

AC XY:

AN XY:

119850

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000971

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000142

AC:

AN:

1410412

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

695314

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000129

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.24e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Aug 27, 2024

The c.712G>A (p.E238K) 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 712, causing the glutamic acid (E) at amino acid position 238 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Uncertain

0.081

BayesDel_noAF

Benign

-0.12

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.48

.;T

Eigen

Benign

0.096

Eigen_PC

Benign

0.16

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.050

MetaRNN

Uncertain

0.62

D;D

MetaSVM

Benign

-0.52

MutationAssessor

Benign

0.86

L;L

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-1.6

N;N

REVEL

Uncertain

0.44

Sift

Benign

0.65

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.87

P;P

Vest4

0.86

MutPred

0.44

Gain of ubiquitination at E238 (P = 0.0039);Gain of ubiquitination at E238 (P = 0.0039);

MVP

0.68

MPC

0.73

ClinPred

0.91

GERP RS

3.7

Varity_R

0.28

gMVP

0.52

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over