Variant 4-70793793-A-G 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_001037442.4(RUFY3):c.1346A>G(p.Gln449Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 11/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

RUFY3
NM_001037442.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.68

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=0.2543671).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUFY3	NM_001037442.4 linkuse as main transcript	c.1346A>G	p.Gln449Arg	missense_variant	13/18	ENST00000381006.8	NP_001032519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUFY3	ENST00000381006.8 linkuse as main transcript	c.1346A>G	p.Gln449Arg	missense_variant	13/18	5	NM_001037442.4	ENSP00000370394	P1	Q7L099-3
RUFY3	ENST00000502653.5 linkuse as main transcript	c.1187A>G	p.Gln396Arg	missense_variant	14/19	2		ENSP00000425400		Q7L099-4
RUFY3	ENST00000504805.6 linkuse as main transcript	c.310A>G	p.Arg104Gly	missense_variant, NMD_transcript_variant	4/6	5		ENSP00000421120
RUFY3	ENST00000512103.5 linkuse as main transcript	c.133+4201A>G		intron_variant, NMD_transcript_variant		3		ENSP00000420980

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250590

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135452

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

Asia WGS

AF:

0.000577

AC:

AN:

3478

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

Feb 28, 2023

The c.1346A>G (p.Q449R) alteration is located in exon 13 (coding exon 13) of the RUFY3 gene. This alteration results from a A to G substitution at nucleotide position 1346, causing the glutamine (Q) at amino acid position 449 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

-0.32

BayesDel_noAF

Benign

-0.61

CADD

Benign

DANN

Benign

0.95

Eigen

Benign

-0.12

Eigen_PC

Benign

0.014

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.55

T;T

M_CAP

Benign

0.0067

MetaRNN

Benign

0.25

T;T

MetaSVM

Benign

-0.95

MutationTaster

Benign

0.57

D;D

PrimateAI

Uncertain

0.57

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.087

Sift

Benign

0.13

T;T

Sift4G

Benign

0.32

T;T

Polyphen

0.18

B;.

Vest4

0.53

MutPred

0.18

Gain of glycosylation at S453 (P = 0.0043);.;

MVP

0.23

MPC

0.082

ClinPred

0.83

GERP RS

3.4

gMVP

0.20

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