Variant 7-99047708-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_ModerateBP6_ModerateBP7BS2

The NM_181349.3(SMURF1):c.1128A>G(p.Glu376=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0027 in 1,614,130 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0028 ( 9 hom. )

Consequence

SMURF1
NM_181349.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.69

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:

TRRAP (HGNC:12347): (transformation/transcription domain associated protein) This gene encodes a large multidomain protein of the phosphoinositide 3-kinase-related kinases (PIKK) family. The encoded protein is a common component of many histone acetyltransferase (HAT) complexes and plays a role in transcription and DNA repair by recruiting HAT complexes to chromatin. Deregulation of this gene may play a role in several types of cancer including glioblastoma multiforme. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Sep 2011]

TRRAP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BP6

Variant 7-99047708-T-C is Benign according to our data. Variant chr7-99047708-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2657718.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.69 with no splicing effect.

BS2

High AC in GnomAd4 at 301 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SMURF1	NM_181349.3 linkuse as main transcript	c.1128A>G	p.Glu376=	synonymous_variant	10/18	ENST00000361368.7	NP_851994.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SMURF1	ENST00000361368.7 linkuse as main transcript	c.1128A>G	p.Glu376=	synonymous_variant	10/18	1	NM_181349.3	ENSP00000355326	P1	Q9HCE7-2
SMURF1	ENST00000361125.1 linkuse as main transcript	c.1206A>G	p.Glu402=	synonymous_variant	11/19	1		ENSP00000354621		Q9HCE7-1
TRRAP	ENST00000468960.3 linkuse as main transcript	n.775T>C		non_coding_transcript_exon_variant	5/5	4
TRRAP	ENST00000482799.3 linkuse as main transcript	n.858T>C		non_coding_transcript_exon_variant	6/6	3

Frequencies

GnomAD3 genomes

AF:

0.00198

AC:

301

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000377

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00359

Gnomad OTH

AF:

0.000957

GnomAD3 exomes

AF:

0.00153

AC:

385

AN:

251482

Hom.:

AF XY:

0.00146

AC XY:

198

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.00141

Gnomad AMR exome

AF:

0.000549

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000508

Gnomad NFE exome

AF:

0.00283

Gnomad OTH exome

AF:

0.00130

GnomAD4 exome

AF:

0.00277

AC:

4053

AN:

1461890

Hom.:

Cov.:

AF XY:

0.00268

AC XY:

1946

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.000626

Gnomad4 ASJ exome

AF:

0.0000765

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.000393

Gnomad4 NFE exome

AF:

0.00342

Gnomad4 OTH exome

AF:

0.00277

GnomAD4 genome

AF:

0.00198

AC:

301

AN:

152240

Hom.:

Cov.:

AF XY:

0.00176

AC XY:

131

AN XY:

74388

show subpopulations

Gnomad4 AFR

AF:

0.000965

Gnomad4 AMR

AF:

0.000589

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000377

Gnomad4 NFE

AF:

0.00359

Gnomad4 OTH

AF:

0.000957

Alfa

AF:

0.00248

Hom.:

Bravo

AF:

0.00216

EpiCase

AF:

0.00376

EpiControl

AF:

0.00314

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

SMURF1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

DANN

Benign

0.76

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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