Variant 4-70783140-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001037442.4(RUFY3):c.944G>A(p.Arg315Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,459,472 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

RUFY3
NM_001037442.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.60

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 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUFY3	NM_001037442.4 linkuse as main transcript	c.944G>A	p.Arg315Gln	missense_variant	9/18	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.944G>A	p.Arg315Gln	missense_variant	9/18	5	NM_001037442.4	ENSP00000370394	P1	Q7L099-3
RUFY3	ENST00000417478.6 linkuse as main transcript	c.1124G>A	p.Arg375Gln	missense_variant	9/12	1		ENSP00000399771		Q7L099-2
RUFY3	ENST00000226328.8 linkuse as main transcript	c.944G>A	p.Arg315Gln	missense_variant	9/13	1		ENSP00000226328		Q7L099-1
RUFY3	ENST00000502653.5 linkuse as main transcript	c.785G>A	p.Arg262Gln	missense_variant	10/19	2		ENSP00000425400		Q7L099-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1459472

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726168

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:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000180

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Jan 26, 2022

The c.944G>A (p.R315Q) alteration is located in exon 9 (coding exon 9) of the RUFY3 gene. This alteration results from a G to A substitution at nucleotide position 944, causing the arginine (R) at amino acid position 315 to be replaced by a glutamine (Q). 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

AlphaMissense

Benign

0.10

BayesDel_addAF

Uncertain

0.16

BayesDel_noAF

Uncertain

-0.010

CADD

Pathogenic

DANN

Uncertain

0.98

DEOGEN2

Benign

0.019

.;.;T;.

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.88

D;D;D;D

M_CAP

Benign

0.039

MetaRNN

Uncertain

0.49

T;T;T;T

MetaSVM

Benign

-0.57

MutationAssessor

Benign

-0.020

.;N;N;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.74

PROVEAN

Benign

1.4

N;N;N;N

REVEL

Uncertain

0.41

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

0.95

T;T;T;T

Polyphen

0.19

B;D;D;.

Vest4

0.75

MutPred

0.18

.;Gain of glycosylation at S320 (P = 0.0091);Gain of glycosylation at S320 (P = 0.0091);.;

MVP

0.63

MPC

2.2

ClinPred

0.80

GERP RS

5.7

Varity_R

0.23

gMVP

0.39

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over