Variant 5-179567556-T-G details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_025158.5(RUFY1):c.698T>G(p.Leu233Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000307 in 1,597,512 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000031 ( 0 hom. )

Consequence

RUFY1
NM_025158.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.75

Variant links:

Genes affected

RUFY1 (HGNC:19760): (RUN and FYVE domain containing 1) This gene encodes a protein that contains a RUN domain and a FYVE-type zinc finger domain. The encoded protein binds to phosphatidylinositol-3-phosphate (PI3P) and plays a role in early endosomal trafficking, tethering and fusion through interactions with small GTPases including Rab4, Rab5 and Rab14. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Dec 2011]

RUFY1 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
RUFY1	NM_025158.5 linkuse as main transcript	c.698T>G	p.Leu233Arg	missense_variant	4/18	ENST00000319449.9	NP_079434.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUFY1	ENST00000319449.9 linkuse as main transcript	c.698T>G	p.Leu233Arg	missense_variant	4/18	1	NM_025158.5	ENSP00000325594		Q96T51-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000167

AC:

AN:

251316

Hom.:

AF XY:

0.000162

AC XY:

AN XY:

135846

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00119

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:

0.000163

GnomAD4 exome

AF:

0.0000311

AC:

AN:

1445182

Hom.:

Cov.:

AF XY:

0.0000319

AC XY:

AN XY:

720094

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00101

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.0000268

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000261

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000680

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.000115

AC:

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

May 15, 2024

The c.698T>G (p.L233R) alteration is located in exon 4 (coding exon 4) of the RUFY1 gene. This alteration results from a T to G substitution at nucleotide position 698, causing the leucine (L) at amino acid position 233 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

AlphaMissense

Uncertain

0.40

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Uncertain

0.070

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.17

T;.;.

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Pathogenic

0.99

M_CAP

Benign

0.026

MetaRNN

Uncertain

0.51

D;D;D

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.3

M;.;.

MutationTaster

Benign

1.0

D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.9

D;D;D

REVEL

Uncertain

0.53

Sift

Uncertain

0.0020

D;D;D

Sift4G

Uncertain

0.017

D;D;D

Polyphen

1.0

D;.;.

Vest4

0.96

MutPred

0.60

Loss of catalytic residue at L233 (P = 0.0047);.;.;

MVP

0.54

MPC

1.0

ClinPred

0.30

GERP RS

5.4

Varity_R

0.87

gMVP

0.82

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