Variant 5-179550801-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_025158.5(RUFY1):c.232T>C(p.Ser78Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000511 in 1,174,916 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000051 ( 0 hom. )

Consequence

RUFY1
NM_025158.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.77

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 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.41911992).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUFY1	NM_025158.5 linkuse as main transcript	c.232T>C	p.Ser78Pro	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.232T>C	p.Ser78Pro	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:

0.00000511

AC:

AN:

1174916

Hom.:

Cov.:

AF XY:

0.00000174

AC XY:

AN XY:

573158

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:

0.00000619

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Aug 20, 2023

The c.232T>C (p.S78P) 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 232, causing the serine (S) at amino acid position 78 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

Benign

0.12

BayesDel_addAF

Benign

-0.024

BayesDel_noAF

Benign

-0.27

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.047

Eigen

Benign

-0.17

Eigen_PC

Benign

-0.13

FATHMM_MKL

Uncertain

0.87

M_CAP

Pathogenic

0.83

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.3

MutationTaster

Benign

0.69

D;D

PrimateAI

Pathogenic

0.93

PROVEAN

Benign

-0.83

REVEL

Benign

0.056

Sift

Uncertain

0.0060

Sift4G

Benign

0.15

Polyphen

0.38

Vest4

0.41

MutPred

0.19

Gain of helix (P = 0.0117);

MVP

0.69

MPC

0.28

ClinPred

0.41

GERP RS

2.8

Varity_R

0.34

gMVP

0.52

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over