Variant chr17-64557641-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The NM_022739.4(SMURF2):c.1398A>G(p.Thr466=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000113 in 1,610,336 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00041 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000082 ( 1 hom. )

Consequence

SMURF2
NM_022739.4 synonymous

Scores

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: -4.35

Variant links:

Genes affected

SMURF2 (HGNC:16809): (SMAD specific E3 ubiquitin protein ligase 2) Enables SMAD binding activity; identical protein binding activity; and ubiquitin-protein transferase activity. Involved in negative regulation of transforming growth factor beta receptor signaling pathway; positive regulation of trophoblast cell migration; and ubiquitin-dependent SMAD protein catabolic process. Located in nuclear speck. Part of ubiquitin ligase complex. [provided by Alliance of Genome Resources, Apr 2022]

SMURF2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BP6

Variant 17-64557641-T-C is Benign according to our data. Variant chr17-64557641-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 3040421.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-4.35 with no splicing effect.

BS2

High AC in GnomAd4 at 63 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
SMURF2	NM_022739.4 linkuse as main transcript	c.1398A>G	p.Thr466=	synonymous_variant	13/19	ENST00000262435.14	NP_073576.1
SMURF2	XM_047436546.1 linkuse as main transcript	c.1404A>G	p.Thr468=	synonymous_variant	13/19		XP_047292502.1
SMURF2	XM_005257585.4 linkuse as main transcript	c.1359A>G	p.Thr453=	synonymous_variant	12/18		XP_005257642.1
SMURF2	XR_007065425.1 linkuse as main transcript	n.4456A>G		non_coding_transcript_exon_variant	13/13

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMURF2	ENST00000262435.14 linkuse as main transcript	c.1398A>G	p.Thr466=	synonymous_variant	13/19	1	NM_022739.4	ENSP00000262435	P1

Frequencies

GnomAD3 genomes

AF:

0.000381

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00128

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000164

AC:

AN:

250182

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

135234

show subpopulations

Gnomad AFR exome

AF:

0.00197

Gnomad AMR exome

AF:

0.000234

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000329

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000816

AC:

119

AN:

1458026

Hom.:

Cov.:

AF XY:

0.0000868

AC XY:

AN XY:

725502

show subpopulations

Gnomad4 AFR exome

AF:

0.00261

Gnomad4 AMR exome

AF:

0.000203

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000466

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.000282

GnomAD4 genome

AF:

0.000414

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74482

show subpopulations

Gnomad4 AFR

AF:

0.00140

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.000292

Hom.:

Bravo

AF:

0.000468

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SMURF2-related disorder

Benign:1

Likely benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 10, 2019

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

1.3

DANN

Benign

0.63

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