Variant chr2-218072449-C-T 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_198483.4(RUFY4):c.229C>T(p.Arg77Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,537,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00014 ( 0 hom. )

Consequence

RUFY4
NM_198483.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.610

Variant links:

Genes affected

RUFY4 (HGNC:24804): (RUN and FYVE domain containing 4) Enables phosphatidylinositol-3-phosphate binding activity. Involved in autophagosome assembly; cellular response to interleukin-4; and positive regulation of macroautophagy. Located in autophagosome. [provided by Alliance of Genome Resources, Apr 2022]

RUFY4 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=0.21086171).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUFY4	NM_198483.4 linkuse as main transcript	c.229C>T	p.Arg77Trp	missense_variant	5/13	ENST00000697321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUFY4	ENST00000697321.1 linkuse as main transcript	c.229C>T	p.Arg77Trp	missense_variant	5/13		NM_198483.4	P1	Q6ZNE9-2

Frequencies

GnomAD3 genomes

AF:

0.0000920

AC:

AN:

152224

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000351

AC:

AN:

142314

Hom.:

AF XY:

0.0000525

AC XY:

AN XY:

76162

show subpopulations

Gnomad AFR exome

AF:

0.000130

Gnomad AMR exome

AF:

0.0000407

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:

0.0000351

Gnomad OTH exome

AF:

0.000234

GnomAD4 exome

AF:

0.000136

AC:

188

AN:

1385030

Hom.:

Cov.:

AF XY:

0.000129

AC XY:

AN XY:

683454

show subpopulations

Gnomad4 AFR exome

AF:

0.0000317

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000379

Gnomad4 FIN exome

AF:

0.0000285

Gnomad4 NFE exome

AF:

0.000166

Gnomad4 OTH exome

AF:

0.0000518

GnomAD4 genome

AF:

0.0000920

AC:

AN:

152224

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74372

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000720

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.000125

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 10, 2024

The c.229C>T (p.R77W) alteration is located in exon 5 (coding exon 3) of the RUFY4 gene. This alteration results from a C to T substitution at nucleotide position 229, causing the arginine (R) at amino acid position 77 to be replaced by a tryptophan (W). 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

0.11

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.049

T;T

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.48

FATHMM_MKL

Benign

0.092

LIST_S2

Benign

0.75

T;T

M_CAP

Benign

0.026

MetaRNN

Benign

0.21

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;M

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.22

PROVEAN

Pathogenic

-5.0

D;D

REVEL

Benign

0.065

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0020

D;D

Vest4

0.34

MutPred

0.61

Gain of catalytic residue at L75 (P = 0.0044);Gain of catalytic residue at L75 (P = 0.0044);

MVP

0.52

MPC

0.20

ClinPred

0.76

GERP RS

2.9

Varity_R

0.26

gMVP

0.37

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