Variant 4-70783135-G-A 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.939G>A(p.Met313Ile) variant causes a missense change. The variant allele was found at a frequency of 0.00000274 in 1,459,850 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

RUFY3
NM_001037442.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.42

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=0.1417886).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUFY3	NM_001037442.4 linkuse as main transcript	c.939G>A	p.Met313Ile	missense_variant	9/18	ENST00000381006.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUFY3	ENST00000381006.8 linkuse as main transcript	c.939G>A	p.Met313Ile	missense_variant	9/18	5	NM_001037442.4	P1	Q7L099-3
RUFY3	ENST00000417478.6 linkuse as main transcript	c.1119G>A	p.Met373Ile	missense_variant	9/12	1			Q7L099-2
RUFY3	ENST00000226328.8 linkuse as main transcript	c.939G>A	p.Met313Ile	missense_variant	9/13	1			Q7L099-1
RUFY3	ENST00000502653.5 linkuse as main transcript	c.780G>A	p.Met260Ile	missense_variant	10/19	2			Q7L099-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000399

AC:

AN:

250630

Hom.:

AF XY:

0.00000738

AC XY:

AN XY:

135510

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000881

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1459850

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726304

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000756

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

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 06, 2024

The c.939G>A (p.M313I) 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 939, causing the methionine (M) at amino acid position 313 to be replaced by an isoleucine (I). 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

Uncertain

0.40

BayesDel_addAF

Uncertain

0.020

BayesDel_noAF

Benign

-0.21

CADD

Uncertain

DANN

Benign

0.97

DEOGEN2

Benign

0.076

.;.;T;.

Eigen

Benign

0.11

Eigen_PC

Uncertain

0.32

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Benign

0.85

D;D;D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.14

T;T;T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

1.1

.;L;L;.

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.75

PROVEAN

Benign

-1.4

N;N;N;N

REVEL

Benign

0.25

Sift

Benign

0.14

T;T;T;T

Sift4G

Benign

0.40

T;T;T;T

Polyphen

0.0030

B;B;B;.

Vest4

0.40

MutPred

0.086

.;Gain of methylation at K317 (P = 0.1187);Gain of methylation at K317 (P = 0.1187);.;

MVP

0.14

MPC

1.0

ClinPred

0.67

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.32

gMVP

0.42

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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