Genetic Variant RUFY1:p.Gly97Ala (chr5-179550859-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_025158.5(RUFY1):c.290G>C(p.Gly97Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000965 in 1,036,034 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 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. G97E) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 9.7e-7 ( 0 hom. )

Consequence

RUFY1
NM_025158.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.679

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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.062299788).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUFY1	NM_025158.5 link	c.290G>C	p.Gly97Ala	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.290G>C	p.Gly97Ala	missense_variant	Exon 1 of 18	1	NM_025158.5	ENSP00000325594.4	Q96T51-1
RUFY1	ENST00000393448.6 link	n.23G>C		non_coding_transcript_exon_variant	Exon 1 of 16	1		ENSP00000377094.2	J3KPP6
RUFY1	ENST00000502984.5 link	c.20G>C	p.Gly7Ala	missense_variant	Exon 1 of 6	3		ENSP00000425533.1	H0Y9Y8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.65e-7

AC:

AN:

1036034

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

491254

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

20668

American (AMR)

AF:

0.00

AC:

AN:

6482

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11716

East Asian (EAS)

AF:

0.00

AC:

AN:

20998

South Asian (SAS)

AF:

0.00

AC:

AN:

20270

European-Finnish (FIN)

AF:

0.00

AC:

AN:

19194

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2646

European-Non Finnish (NFE)

AF:

0.00000112

AC:

AN:

894298

Other (OTH)

AF:

0.00

AC:

AN:

39762

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.53

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.020

Eigen

Benign

-0.61

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.066

M_CAP

Benign

0.067

MetaRNN

Benign

0.062

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.7

PhyloP100

-0.68

PrimateAI

Uncertain

0.74

PROVEAN

Benign

-0.030

REVEL

Benign

0.043

Sift

Benign

0.34

Sift4G

Benign

0.49

Polyphen

0.0

Vest4

0.096

MutPred

0.25

Loss of catalytic residue at G97 (P = 0.0093);

MVP

0.48

MPC

0.29

ClinPred

0.10

GERP RS

-2.2

PromoterAI

-0.011

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.3

Varity_R

0.052

gMVP

0.21

Mutation Taster

=98/2

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