Variant 4-70705045-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001130709.2(RUFY3):c.109G>C(p.Gly37Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000157 in 1,248,498 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 9/14 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

RUFY3
NM_001130709.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.58

Variant links:

Genes affected

RUFY3 (HGNC:30285): (RUN and FYVE domain containing 3) This gene encodes a RPIP8, UNC-14, and NESCA domain-containing protein that is required for maintenance of neuronal polarity. In addition, it has been implicated in mediation of gastric cancer cell migration and invasion via interaction with P21-activated kinase-1, which promotes its expression. The encoded protein localizes to F-actin-enriched invadopodia to induce formation of protrusions, thereby facilitating cell migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

RUFY3 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.090271086).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	Protein	UniProt
RUFY3	NM_001130709.2 link	c.109G>C	p.Gly37Arg	missense_variant	1/12	NP_001124181.1	Q7L099-2
RUFY3	XM_011531750.3 link	c.109G>C	p.Gly37Arg	missense_variant	2/19	XP_011530052.1
RUFY3	XM_047449825.1 link	c.109G>C	p.Gly37Arg	missense_variant	1/18	XP_047305781.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	Protein	UniProt
RUFY3	ENST00000417478.6 link	c.109G>C	p.Gly37Arg	missense_variant	1/12	1	ENSP00000399771.2	Q7L099-2
RUFY3	ENST00000514898.1 link	c.109G>C	p.Gly37Arg	missense_variant	2/2	4	ENSP00000426165.1	D6RH24
RUFY3	ENST00000503876.5 link	c.-15+570G>C		intron_variant		4	ENSP00000426734.1	D6REM9

Frequencies

GnomAD3 genomes

AF:

0.0000330

AC:

AN:

151322

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000738

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000174

AC:

191

AN:

1097176

Hom.:

Cov.:

AF XY:

0.000189

AC XY:

AN XY:

524324

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:

0.0000371

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000202

Gnomad4 OTH exome

AF:

0.0000460

GnomAD4 genome

AF:

0.0000330

AC:

AN:

151322

Hom.:

Cov.:

AF XY:

0.0000271

AC XY:

AN XY:

73884

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000738

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000264

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

Sep 01, 2021

The c.109G>C (p.G37R) alteration is located in exon 1 (coding exon 1) of the RUFY3 gene. This alteration results from a G to C substitution at nucleotide position 109, causing the glycine (G) at amino acid position 37 to be replaced by an arginine (R). 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

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.58

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.078

T;.

Eigen

Benign

-0.76

Eigen_PC

Benign

-0.80

FATHMM_MKL

Benign

0.0087

LIST_S2

Benign

0.62

T;T

M_CAP

Benign

0.027

MetaRNN

Benign

0.090

T;T

MetaSVM

Benign

-1.0

PROVEAN

Pathogenic

-7.1

D;N

REVEL

Benign

0.045

Sift

Uncertain

0.010

D;D

Sift4G

Uncertain

0.025

D;D

Polyphen

0.0

.;B

Vest4

0.095

MutPred

0.24

Gain of glycosylation at T38 (P = 0.013);Gain of glycosylation at T38 (P = 0.013);

MVP

0.18

ClinPred

0.78

GERP RS

2.3

Splicing

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