Genetic Variant RUFY1:p.Ala103Ser (chr5-179550876-G-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_025158.5(RUFY1):c.307G>T(p.Ala103Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A103T) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RUFY1
NM_025158.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.647

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.11089894).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUFY1	NM_025158.5 link	c.307G>T	p.Ala103Ser	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.307G>T	p.Ala103Ser	missense_variant	Exon 1 of 18	1	NM_025158.5	ENSP00000325594.4	Q96T51-1
RUFY1	ENST00000393448.6 link	n.40G>T		non_coding_transcript_exon_variant	Exon 1 of 16	1		ENSP00000377094.2	J3KPP6
RUFY1	ENST00000502984.5 link	c.37G>T	p.Ala13Ser	missense_variant	Exon 1 of 6	3		ENSP00000425533.1	H0Y9Y8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1016162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

480650

African (AFR)

AF:

0.00

AC:

AN:

20058

American (AMR)

AF:

0.00

AC:

AN:

5958

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11046

East Asian (EAS)

AF:

0.00

AC:

AN:

19122

South Asian (SAS)

AF:

0.00

AC:

AN:

19558

European-Finnish (FIN)

AF:

0.00

AC:

AN:

17930

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2542

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

881450

Other (OTH)

AF:

0.00

AC:

AN:

38498

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.96

DEOGEN2

Benign

0.019

Eigen

Benign

-0.54

Eigen_PC

Benign

-0.39

FATHMM_MKL

Benign

0.69

M_CAP

Pathogenic

0.49

MetaRNN

Benign

0.11

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.4

PhyloP100

0.65

PrimateAI

Uncertain

0.70

PROVEAN

Benign

0.16

REVEL

Benign

0.091

Sift

Benign

0.32

Sift4G

Benign

0.78

Polyphen

0.0

Vest4

0.18

MutPred

0.086

Gain of phosphorylation at A103 (P = 0.0248);

MVP

0.49

MPC

0.20

ClinPred

0.11

GERP RS

2.1

PromoterAI

0.0061

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.9

Varity_R

0.058

gMVP

0.25

Mutation Taster

=91/9

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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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over