7-99042136-C-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_Moderate BP6_Moderate BP7 BS2

The NM_181349.3(SMURF1):c.1353G>A(p.Pro451=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000438 in 1,613,418 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 (★).

• Frequency:
  • Genomes: 𝑓 0.00037 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00045 (1 hom.)
• Consequence: SMURF1 NM_181349.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.497

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]

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]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BP6: Variant 7-99042136-C-T is Benign according to our data. Variant chr7-99042136-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2657717.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.497 with no splicing effect.
• BS2: High AC in GnomAd at 56 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SMURF1	NM_181349.3	c.1353G>A	p.Pro451=	synonymous_variant	12/18	ENST00000361368.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SMURF1	ENST00000361368.7	c.1353G>A	p.Pro451=	synonymous_variant	12/18	1	NM_181349.3	P1
SMURF1	ENST00000361125.1	c.1431G>A	p.Pro477=	synonymous_variant	13/19	1
TRRAP	ENST00000468960.3	n.722-5519C>T		intron_variant, non_coding_transcript_variant		4
TRRAP	ENST00000482799.3	n.554-3406C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.000368 AC: 56 AN: 152096 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000967

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000559

Gnomad OTH AF: 0.00192

GnomAD3 exomes AF: 0.000430 AC: 108 AN: 251216 Hom.: 0 AF XY: 0.000471 AC XY: 64 AN XY: 135762

Gnomad AFR exome AF: 0.000123

Gnomad AMR exome AF: 0.000261

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.000819

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000572

Gnomad OTH exome AF: 0.000816

GnomAD4 exome AF: 0.000446 AC: 651 AN: 1461204 Hom.: 1 Cov.: 31 AF XY: 0.000466 AC XY: 339 AN XY: 726924

Gnomad4 AFR exome AF: 0.0000598

Gnomad4 AMR exome AF: 0.000201

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000592

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000488

Gnomad4 OTH exome AF: 0.000398

GnomAD4 genome AF: 0.000368 AC: 56 AN: 152214 Hom.: 0 Cov.: 32 AF XY: 0.000443 AC XY: 33 AN XY: 74416

Gnomad4 AFR AF: 0.0000964

Gnomad4 AMR AF: 0.000262

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000559

Gnomad4 OTH AF: 0.00190

Alfa AF: 0.000630 Hom.: 1

Bravo AF: 0.000363

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00115

EpiControl AF: 0.000474

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2023

SMURF1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
Cadd	Benign	7.5
Dann	Benign	0.86

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

Other links and lift over

dbSNP: rs149320056; hg19: chr7-98639759;