Variant chr2-218072411-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_198483.4(RUFY4):c.191G>C(p.Arg64Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000095 in 1,537,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00054 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

RUFY4
NM_198483.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.938

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06528127).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUFY4	NM_198483.4 linkuse as main transcript	c.191G>C	p.Arg64Pro	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.191G>C	p.Arg64Pro	missense_variant	5/13		NM_198483.4	P1	Q6ZNE9-2

Frequencies

GnomAD3 genomes

AF:

0.000539

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

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:

0.00316

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000120

AC:

AN:

142184

Hom.:

AF XY:

0.000158

AC XY:

AN XY:

76104

show subpopulations

Gnomad AFR exome

AF:

0.00210

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.000119

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

AF:

0.0000462

AC:

AN:

1385084

Hom.:

Cov.:

AF XY:

0.0000454

AC XY:

AN XY:

683478

show subpopulations

Gnomad4 AFR exome

AF:

0.00161

Gnomad4 AMR exome

AF:

0.0000280

Gnomad4 ASJ exome

AF:

0.0000397

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000463

Gnomad4 OTH exome

AF:

0.000104

GnomAD4 genome

AF:

0.000538

AC:

AN:

152306

Hom.:

Cov.:

AF XY:

0.000470

AC XY:

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.00185

Gnomad4 AMR

AF:

0.000262

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

Bravo

AF:

0.000672

ExAC

AF:

0.0000417

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

Aug 30, 2021

The c.191G>C (p.R64P) alteration is located in exon 5 (coding exon 3) of the RUFY4 gene. This alteration results from a G to C substitution at nucleotide position 191, causing the arginine (R) at amino acid position 64 to be replaced by a proline (P). 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

0.27

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.043

T;T

Eigen

Benign

-0.052

Eigen_PC

Benign

-0.077

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.74

T;T

M_CAP

Benign

0.0075

MetaRNN

Benign

0.065

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

.;L

MutationTaster

Benign

0.96

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-5.5

D;D

REVEL

Benign

0.16

Sift

Uncertain

0.0020

D;D

Sift4G

Uncertain

0.0050

D;D

Vest4

0.43

MutPred

0.64

Gain of catalytic residue at P63 (P = 0.0164);Gain of catalytic residue at P63 (P = 0.0164);

MVP

0.45

MPC

0.067

ClinPred

0.23

GERP RS

1.9

Varity_R

0.67

gMVP

0.53

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