Genetic Variant RUFY1:p.Ser78Leu (chr5-179550802-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_025158.5(RUFY1):c.233C>T(p.Ser78Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000856 in 1,168,590 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. S78P) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 8.6e-7 ( 0 hom. )

Consequence

RUFY1
NM_025158.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.69

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.40044487).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUFY1	NM_025158.5 link	c.233C>T	p.Ser78Leu	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.233C>T	p.Ser78Leu	missense_variant	Exon 1 of 18	1	NM_025158.5	ENSP00000325594.4	Q96T51-1
RUFY1	ENST00000393448.6 link	n.-35C>T		upstream_gene_variant		1		ENSP00000377094.2	J3KPP6
RUFY1	ENST00000502984.5 link	c.-38C>T		upstream_gene_variant		3		ENSP00000425533.1	H0Y9Y8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000254

AC:

AN:

39364

AF XY:

0.0000411

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000214

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

8.56e-7

AC:

AN:

1168590

Hom.:

Cov.:

AF XY:

0.00000176

AC XY:

AN XY:

569590

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23724

American (AMR)

AF:

0.0000695

AC:

AN:

14396

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17588

East Asian (EAS)

AF:

0.00

AC:

AN:

25446

South Asian (SAS)

AF:

0.00

AC:

AN:

45040

European-Finnish (FIN)

AF:

0.00

AC:

AN:

26290

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3462

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

966186

Other (OTH)

AF:

0.00

AC:

AN:

46458

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.775

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.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.067

BayesDel_noAF

Benign

-0.33

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.055

Eigen

Benign

-0.019

Eigen_PC

Benign

0.073

FATHMM_MKL

Uncertain

0.95

M_CAP

Pathogenic

0.88

MetaRNN

Benign

0.40

MetaSVM

Benign

-0.67

MutationAssessor

Uncertain

2.3

PhyloP100

3.7

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-1.9

REVEL

Benign

0.067

Sift

Uncertain

0.0040

Sift4G

Benign

0.20

Polyphen

0.20

Vest4

0.35

MutPred

0.27

Gain of helix (P = 0.0078);

MVP

0.70

MPC

0.21

ClinPred

0.51

GERP RS

4.0

PromoterAI

-0.0035

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.28

gMVP

0.50

Mutation Taster

=77/23

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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5-179550802-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over