dbSNP rs541260898: RUFY1:p.Arg51Gly (chr5-179550720-C-G) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_025158.5(RUFY1):c.151C>G(p.Arg51Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,482,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000047 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 0 hom. )

Consequence

RUFY1
NM_025158.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.715

Publications

0 publications found

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:

LOC128966623 (HGNC:):

LOC128966623 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.05026564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUFY1	NM_025158.5 link	c.151C>G	p.Arg51Gly	missense_variant	Exon 1 of 18	ENST00000319449.9	NP_079434.3	Q96T51-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
RUFY1	ENST00000319449.9 link	c.151C>G	p.Arg51Gly	missense_variant	Exon 1 of 18	1	NM_025158.5	ENSP00000325594.4	Q96T51-1
RUFY1	ENST00000393448.6 link	n.-117C>G		upstream_gene_variant		1		ENSP00000377094.2	J3KPP6
RUFY1	ENST00000502984.5 link	c.-120C>G		upstream_gene_variant		3		ENSP00000425533.1	H0Y9Y8

Frequencies

GnomAD3 genomes

AF:

0.0000466

AC:

AN:

150366

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:

0.000104

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000700

AC:

AN:

114328

AF XY:

0.0000764

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000486

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000101

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000157

AC:

209

AN:

1332282

Hom.:

Cov.:

AF XY:

0.000158

AC XY:

104

AN XY:

659964

show subpopulations

African (AFR)

AF:

0.0000366

AC:

AN:

27346

American (AMR)

AF:

0.0000635

AC:

AN:

31510

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22926

East Asian (EAS)

AF:

0.00

AC:

AN:

29228

South Asian (SAS)

AF:

0.0000673

AC:

AN:

74330

European-Finnish (FIN)

AF:

0.0000298

AC:

AN:

33544

Middle Eastern (MID)

AF:

0.000196

AC:

AN:

5090

European-Non Finnish (NFE)

AF:

0.000185

AC:

195

AN:

1053782

Other (OTH)

AF:

0.0000734

AC:

AN:

54526

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000465

AC:

AN:

150474

Hom.:

Cov.:

AF XY:

0.0000408

AC XY:

AN XY:

73484

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41336

American (AMR)

AF:

0.00

AC:

AN:

15128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3440

East Asian (EAS)

AF:

0.00

AC:

AN:

5146

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9902

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.000104

AC:

AN:

67398

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.582

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000142

Hom.:

Bravo

AF:

0.0000793

ExAC

AF:

0.0000555

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.151C>G (p.R51G) alteration is located in exon 1 (coding exon 1) of the RUFY1 gene. This alteration results from a C to G substitution at nucleotide position 151, causing the arginine (R) at amino acid position 51 to be replaced by a glycine (G). 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

0.064

BayesDel_addAF

Benign

-0.33

BayesDel_noAF

Benign

-0.51

CADD

Benign

(source)

DANN

Benign

0.51

DEOGEN2

Benign

0.021

Eigen

Benign

-0.93

Eigen_PC

Benign

-0.93

FATHMM_MKL

Benign

0.18

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.2

PhyloP100

0.71

PrimateAI

Pathogenic

0.81

PROVEAN

Benign

-0.85

REVEL

Benign

0.036

Sift

Benign

0.38

Sift4G

Benign

0.37

Polyphen

0.020

Vest4

0.20

MutPred

0.29

Gain of loop (P = 3e-04);

MVP

0.51

MPC

0.28

ClinPred

0.056

GERP RS

2.9

PromoterAI

-0.0034

Neutral

(source)

Varity_R

0.16

gMVP

0.27

Mutation Taster

=93/7

polymorphism

(source)

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

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rs541260898

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over