Variant 2-109129714-C-T 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_001099289.3(SH3RF3):c.174C>T(p.Ser58Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00106 in 1,537,260 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0010 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0011 ( 5 hom. )

Consequence

SH3RF3
NM_001099289.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.211

Variant links:

Genes affected

SH3RF3 (HGNC:24699): (SH3 domain containing ring finger 3) Enables ubiquitin protein ligase activity. Involved in positive regulation of JNK cascade and protein autoubiquitination. [provided by Alliance of Genome Resources, Apr 2022]

SH3RF3 links:

RANBP2 (HGNC:9848): (RAN binding protein 2) RAN is a small GTP-binding protein of the RAS superfamily that is associated with the nuclear membrane and is thought to control a variety of cellular functions through its interactions with other proteins. This gene encodes a very large RAN-binding protein that immunolocalizes to the nuclear pore complex. The protein is a giant scaffold and mosaic cyclophilin-related nucleoporin implicated in the Ran-GTPase cycle. The encoded protein directly interacts with the E2 enzyme UBC9 and strongly enhances SUMO1 transfer from UBC9 to the SUMO1 target SP100. These findings place sumoylation at the cytoplasmic filaments of the nuclear pore complex and suggest that, for some substrates, modification and nuclear import are linked events. This gene is partially duplicated in a gene cluster that lies in a hot spot for recombination on chromosome 2q. [provided by RefSeq, Jul 2008]

RANBP2 links:

SH3RF3-AS1 (HGNC:):

SH3RF3-AS1 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=-0.43).

BP6

Variant 2-109129714-C-T is Benign according to our data. Variant chr2-109129714-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2651260.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.211 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 5 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SH3RF3	NM_001099289.3 linkuse as main transcript	c.174C>T	p.Ser58Ser	synonymous_variant	1/10	ENST00000309415.8	NP_001092759.1	Q8TEJ3
SH3RF3	XM_011511109.3 linkuse as main transcript	c.174C>T	p.Ser58Ser	synonymous_variant	1/9		XP_011509411.1
RANBP2	XM_047445367.1 linkuse as main transcript	c.8370+356668C>T		intron_variant			XP_047301323.1
SH3RF3-AS1	NR_029193.1 linkuse as main transcript	n.406G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SH3RF3	ENST00000309415.8 linkuse as main transcript	c.174C>T	p.Ser58Ser	synonymous_variant	1/10	5	NM_001099289.3	ENSP00000309186.6		Q8TEJ3

Frequencies

GnomAD3 genomes

AF:

0.00101

AC:

153

AN:

152012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.000577

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00393

Gnomad FIN

AF:

0.000473

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00159

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.00146

AC:

204

AN:

139678

Hom.:

AF XY:

0.00176

AC XY:

133

AN XY:

75440

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000636

Gnomad ASJ exome

AF:

0.000361

Gnomad EAS exome

AF:

0.0000960

Gnomad SAS exome

AF:

0.00403

Gnomad FIN exome

AF:

0.000929

Gnomad NFE exome

AF:

0.00148

Gnomad OTH exome

AF:

0.00171

GnomAD4 exome

AF:

0.00106

AC:

1473

AN:

1385140

Hom.:

Cov.:

AF XY:

0.00122

AC XY:

833

AN XY:

683492

show subpopulations

Gnomad4 AFR exome

AF:

0.0000648

Gnomad4 AMR exome

AF:

0.000540

Gnomad4 ASJ exome

AF:

0.000519

Gnomad4 EAS exome

AF:

0.0000283

Gnomad4 SAS exome

AF:

0.00382

Gnomad4 FIN exome

AF:

0.000921

Gnomad4 NFE exome

AF:

0.000928

Gnomad4 OTH exome

AF:

0.00147

GnomAD4 genome

AF:

0.00101

AC:

153

AN:

152120

Hom.:

Cov.:

AF XY:

0.000887

AC XY:

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000523

Gnomad4 ASJ

AF:

0.000577

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.00394

Gnomad4 FIN

AF:

0.000473

Gnomad4 NFE

AF:

0.00159

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.00147

Hom.:

Bravo

AF:

0.000820

Asia WGS

AF:

0.00203

AC:

AN:

3454

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

Sep 01, 2022

SH3RF3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Benign

0.87

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