dbSNP rs1761788224: RUFY1:p.Ala73Val (chr5-179550787-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 3 ACMG points: 3P and 0B. PM2PP3

The NM_025158.5(RUFY1):c.218C>T(p.Ala73Val) variant causes a missense change. The variant allele was found at a frequency of 0.000000831 in 1,203,794 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: not found (cov: 33)

Exomes 𝑓: 8.3e-7 ( 0 hom. )

Consequence

RUFY1
NM_025158.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.91

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:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.797

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUFY1	NM_025158.5 link	c.218C>T	p.Ala73Val	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.218C>T	p.Ala73Val	missense_variant	Exon 1 of 18	1	NM_025158.5	ENSP00000325594.4	Q96T51-1
RUFY1	ENST00000393448.6 link	n.-50C>T		upstream_gene_variant		1		ENSP00000377094.2	J3KPP6
RUFY1	ENST00000502984.5 link	c.-53C>T		upstream_gene_variant		3		ENSP00000425533.1	H0Y9Y8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

8.31e-7

AC:

AN:

1203794

Hom.:

Cov.:

AF XY:

0.00000170

AC XY:

AN XY:

589460

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

24550

American (AMR)

AF:

0.0000558

AC:

AN:

17918

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19520

East Asian (EAS)

AF:

0.00

AC:

AN:

26044

South Asian (SAS)

AF:

0.00

AC:

AN:

53586

European-Finnish (FIN)

AF:

0.00

AC:

AN:

27998

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3782

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

982344

Other (OTH)

AF:

0.00

AC:

AN:

48052

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 25, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.218C>T (p.A73V) alteration is located in exon 1 (coding exon 1) of the RUFY1 gene. This alteration results from a C to T substitution at nucleotide position 218, causing the alanine (A) at amino acid position 73 to be replaced by a valine (V). 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

Pathogenic

0.59

BayesDel_addAF

Benign

-0.057

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.057

Eigen

Uncertain

0.32

Eigen_PC

Benign

0.22

FATHMM_MKL

Uncertain

0.95

M_CAP

Pathogenic

0.82

MetaRNN

Pathogenic

0.80

MetaSVM

Benign

-0.52

MutationAssessor

Uncertain

2.4

PhyloP100

3.9

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.11

REVEL

Benign

0.13

Sift

Uncertain

0.0050

Sift4G

Uncertain

0.015

Polyphen

0.99

Vest4

0.63

MutPred

0.29

Loss of disorder (P = 0.0872);

MVP

0.79

MPC

0.82

ClinPred

0.97

GERP RS

3.3

PromoterAI

0.0029

Neutral

(source)

Varity_R

0.20

gMVP

0.65

Mutation Taster

=89/11

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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rs1761788224

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over