Variant 2-218072816-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_198483.4(RUFY4):c.317G>A(p.Arg106His) variant causes a missense change. The variant allele was found at a frequency of 0.0000514 in 1,535,766 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 0 hom. )

Consequence

RUFY4
NM_198483.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.60

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 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.873

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUFY4	NM_198483.4 linkuse as main transcript	c.317G>A	p.Arg106His	missense_variant	6/13	ENST00000697321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUFY4	ENST00000697321.1 linkuse as main transcript	c.317G>A	p.Arg106His	missense_variant	6/13		NM_198483.4	P1	Q6ZNE9-2
RUFY4	ENST00000374155.7 linkuse as main transcript	c.317G>A	p.Arg106His	missense_variant	5/12	2
RUFY4	ENST00000344321.8 linkuse as main transcript	c.317G>A	p.Arg106His	missense_variant	4/11	5		P1	Q6ZNE9-2
RUFY4	ENST00000457754.6 linkuse as main transcript	c.279+317G>A		intron_variant, NMD_transcript_variant		2			Q6ZNE9-3

Frequencies

GnomAD3 genomes

AF:

0.0000526

AC:

AN:

152152

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000588

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000513

AC:

AN:

1383614

Hom.:

Cov.:

AF XY:

0.0000425

AC XY:

AN XY:

682686

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:

0.0000127

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000631

Gnomad4 OTH exome

AF:

0.0000346

GnomAD4 genome

AF:

0.0000526

AC:

AN:

152152

Hom.:

Cov.:

AF XY:

0.0000807

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.0000724

Gnomad4 AMR

AF:

0.0000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000588

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000302

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

Dec 02, 2022

The c.317G>A (p.R106H) alteration is located in exon 6 (coding exon 4) of the RUFY4 gene. This alteration results from a G to A substitution at nucleotide position 317, causing the arginine (R) at amino acid position 106 to be replaced by a histidine (H). 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

0.50

BayesDel_addAF

Pathogenic

0.26

BayesDel_noAF

Pathogenic

0.14

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.072

T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.51

FATHMM_MKL

Uncertain

0.91

LIST_S2

Uncertain

0.91

D;D

M_CAP

Benign

0.062

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Benign

-0.60

MutationAssessor

Pathogenic

3.0

.;M

MutationTaster

Benign

0.90

D;D;D

PrimateAI

Uncertain

0.63

PROVEAN

Pathogenic

-4.6

D;D

REVEL

Uncertain

0.44

Sift

Uncertain

0.0010

D;D

Sift4G

Pathogenic

0.0

D;D

Vest4

0.73

MutPred

0.78

Loss of MoRF binding (P = 0.005);Loss of MoRF binding (P = 0.005);

MVP

0.57

MPC

0.24

ClinPred

0.93

GERP RS

4.1

Varity_R

0.68

gMVP

0.76

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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