Variant 5-179550799-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_025158.5(RUFY1):c.230T>C(p.Leu77Pro) variant causes a missense change. The variant allele was found at a frequency of 0.0000135 in 1,182,802 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: 0.000014 ( 0 hom. )

Consequence

RUFY1
NM_025158.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.94

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.777

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUFY1	NM_025158.5 linkuse as main transcript	c.230T>C	p.Leu77Pro	missense_variant	1/18	ENST00000319449.9	NP_079434.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RUFY1	ENST00000319449.9 linkuse as main transcript	c.230T>C	p.Leu77Pro	missense_variant	1/18	1	NM_025158.5	ENSP00000325594	Q96T51-1
RUFY1	ENST00000393448.6 linkuse as main transcript			upstream_gene_variant		1		ENSP00000377094
RUFY1	ENST00000502984.5 linkuse as main transcript			upstream_gene_variant		3		ENSP00000425533

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.0000135

AC:

AN:

1182802

Hom.:

Cov.:

AF XY:

0.0000121

AC XY:

AN XY:

577724

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.0000213

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 08, 2023

The c.230T>C (p.L77P) alteration is located in exon 1 (coding exon 1) of the RUFY1 gene. This alteration results from a T to C substitution at nucleotide position 230, causing the leucine (L) at amino acid position 77 to be replaced by a proline (P). 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

Uncertain

0.42

BayesDel_addAF

Benign

-0.030

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.038

Eigen

Uncertain

0.24

Eigen_PC

Uncertain

0.23

FATHMM_MKL

Uncertain

0.94

M_CAP

Pathogenic

0.84

MetaRNN

Pathogenic

0.78

MetaSVM

Benign

-0.73

MutationAssessor

Uncertain

2.0

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.79

REVEL

Benign

0.076

Sift

Uncertain

0.0080

Sift4G

Uncertain

0.016

Polyphen

0.89

Vest4

0.77

MutPred

0.28

Loss of helix (P = 0.0196);

MVP

0.71

MPC

0.92

ClinPred

0.12

GERP RS

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.47

gMVP

0.64

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over