Variant chr2-218075094-T-G 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.602T>G(p.Ile201Ser) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000105 in 1,521,338 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/24 in silico tools predict a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000010 ( 0 hom. )

Consequence

RUFY4
NM_198483.4 missense, splice_region

Scores

Splicing: ADA: 0.06002

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.74

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=0.26319185).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUFY4	NM_198483.4 linkuse as main transcript	c.602T>G	p.Ile201Ser	missense_variant, splice_region_variant	9/13	ENST00000697321.1	NP_940885.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUFY4	ENST00000697321.1 linkuse as main transcript	c.602T>G	p.Ile201Ser	missense_variant, splice_region_variant	9/13		NM_198483.4	ENSP00000513250	P1	Q6ZNE9-2

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

152070

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0000102

AC:

AN:

1369268

Hom.:

Cov.:

AF XY:

0.00000894

AC XY:

AN XY:

671254

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:

0.0000132

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000132

AC:

AN:

152070

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74282

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000573

Hom.:

Bravo

AF:

0.0000151

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

Jul 25, 2023

The c.602T>G (p.I201S) alteration is located in exon 9 (coding exon 7) of the RUFY4 gene. This alteration results from a T to G substitution at nucleotide position 602, causing the isoleucine (I) at amino acid position 201 to be replaced by a serine (S). 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

0.19

BayesDel_addAF

Benign

-0.041

BayesDel_noAF

Benign

-0.30

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.016

T;T

Eigen

Benign

0.0091

Eigen_PC

Benign

-0.073

FATHMM_MKL

Benign

0.61

LIST_S2

Benign

0.32

T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.26

T;T

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.97

.;L

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.39

PROVEAN

Benign

-0.050

N;D

REVEL

Benign

0.18

Sift

Uncertain

0.0030

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

.;D

Vest4

0.63

MVP

0.68

MPC

0.21

ClinPred

0.83

GERP RS

4.2

Varity_R

0.37

gMVP

0.22

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.060

dbscSNV1_RF

Benign

0.36

SpliceAI score (max)

0.24

Details are displayed if max score is > 0.2

DS_AL_spliceai

0.24

Position offset: -1

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