dbSNP rs759909384: RUFY1:p.Asp98Asn (chr5-179550861-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_025158.5(RUFY1):c.292G>A(p.Asp98Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000287 in 1,186,202 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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: 0.000026 ( 0 hom. )

Consequence

RUFY1
NM_025158.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.98

Publications

1 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 -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14673844).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUFY1	NM_025158.5 link	c.292G>A	p.Asp98Asn	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.292G>A	p.Asp98Asn	missense_variant	Exon 1 of 18	1	NM_025158.5	ENSP00000325594.4	Q96T51-1
RUFY1	ENST00000393448.6 link	n.25G>A		non_coding_transcript_exon_variant	Exon 1 of 16	1		ENSP00000377094.2	J3KPP6
RUFY1	ENST00000502984.5 link	c.22G>A	p.Asp8Asn	missense_variant	Exon 1 of 6	3		ENSP00000425533.1	H0Y9Y8

Frequencies

GnomAD3 genomes

AF:

0.0000466

AC:

AN:

150258

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000297

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

142

AF XY:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000261

AC:

AN:

1035836

Hom.:

Cov.:

AF XY:

0.0000244

AC XY:

AN XY:

491154

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20672

American (AMR)

AF:

0.00

AC:

AN:

6480

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11712

East Asian (EAS)

AF:

0.000286

AC:

AN:

21004

South Asian (SAS)

AF:

0.000593

AC:

AN:

20242

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19182

Middle Eastern (MID)

AF:

0.000378

AC:

AN:

2644

European-Non Finnish (NFE)

AF:

0.00000783

AC:

AN:

894168

Other (OTH)

AF:

0.0000252

AC:

AN:

39732

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.534

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000466

AC:

AN:

150366

Hom.:

Cov.:

AF XY:

0.0000681

AC XY:

AN XY:

73468

show subpopulations

African (AFR)

AF:

0.0000242

AC:

AN:

41342

American (AMR)

AF:

0.00

AC:

AN:

15100

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3454

East Asian (EAS)

AF:

0.000387

AC:

AN:

5162

South Asian (SAS)

AF:

0.000414

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9786

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000297

AC:

AN:

67408

Other (OTH)

AF:

0.00

AC:

AN:

2082

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000712

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.00102

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 19, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.292G>A (p.D98N) alteration is located in exon 1 (coding exon 1) of the RUFY1 gene. This alteration results from a G to A substitution at nucleotide position 292, causing the aspartic acid (D) at amino acid position 98 to be replaced by an asparagine (N). 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

0.083

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.045

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.83

M_CAP

Pathogenic

0.63

MetaRNN

Benign

0.15

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.81

PhyloP100

4.0

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-1.3

REVEL

Benign

0.091

Sift

Benign

0.20

Sift4G

Benign

0.27

Polyphen

0.079

Vest4

0.35

MutPred

0.16

Loss of loop (P = 0.0203);

MVP

0.56

MPC

0.24

ClinPred

0.59

GERP RS

4.0

PromoterAI

-0.023

Neutral

(source)

Varity_R

0.16

gMVP

0.27

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

rs759909384

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