5-179550720-C-G

Variant names:

• chr5-179550720-C-G
• rs541260898
• NM_025158.5:c.151C>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_025158.5(RUFY1):​c.151C>G​(p.Arg51Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000146 in 1,482,756 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000047 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: RUFY1 NM_025158.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.715
• Publications: 0 publications found

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]

LOC128966623 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05026564).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUFY1	NM_025158.5	c.151C>G	p.Arg51Gly	missense_variant	Exon 1 of 18	ENST00000319449.9	NP_079434.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUFY1	ENST00000319449.9	c.151C>G	p.Arg51Gly	missense_variant	Exon 1 of 18	1	NM_025158.5	ENSP00000325594.4
RUFY1	ENST00000393448.6	n.-117C>G		upstream_gene_variant		1		ENSP00000377094.2
RUFY1	ENST00000502984.5	c.-120C>G		upstream_gene_variant		3		ENSP00000425533.1

Frequencies

GnomAD3 genomes AF: 0.0000466 AC: 7 AN: 150366 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000104

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000700 AC: 8 AN: 114328 AF XY: 0.0000764

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000486

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000101

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000157 AC: 209 AN: 1332282 Hom.: 0 Cov.: 35 AF XY: 0.000158 AC XY: 104 AN XY: 659964

African (AFR) AF: 0.0000366 AC: 1 AN: 27346

American (AMR) AF: 0.0000635 AC: 2 AN: 31510

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22926

East Asian (EAS) AF: 0.00 AC: 0 AN: 29228

South Asian (SAS) AF: 0.0000673 AC: 5 AN: 74330

European-Finnish (FIN) AF: 0.0000298 AC: 1 AN: 33544

Middle Eastern (MID) AF: 0.000196 AC: 1 AN: 5090

European-Non Finnish (NFE) AF: 0.000185 AC: 195 AN: 1053782

Other (OTH) AF: 0.0000734 AC: 4 AN: 54526

GnomAD4 genome AF: 0.0000465 AC: 7 AN: 150474 Hom.: 0 Cov.: 33 AF XY: 0.0000408 AC XY: 3 AN XY: 73484

African (AFR) AF: 0.00 AC: 0 AN: 41336

American (AMR) AF: 0.00 AC: 0 AN: 15128

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3440

East Asian (EAS) AF: 0.00 AC: 0 AN: 5146

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9902

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.000104 AC: 7 AN: 67398

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.0000793

ExAC AF: 0.0000555 AC: 6

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.151C>G (p.R51G) alteration is located in exon 1 (coding exon 1) of the RUFY1 gene. This alteration results from a C to G substitution at nucleotide position 151, causing the arginine (R) at amino acid position 51 to be replaced by a glycine (G). 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	0.064
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	17
DANN	Benign	0.51
DEOGEN2	Benign	0.021	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-0.93
FATHMM_MKL	Benign	0.18	N
M_CAP	Pathogenic	0.37	D
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.71
PrimateAI	Pathogenic	0.81	D
PROVEAN	Benign	-0.85	N
REVEL	Benign	0.036
Sift	Benign	0.38	T
Sift4G	Benign	0.37	T
Polyphen		0.020	B
Vest4		0.20
MutPred		0.29		Gain of loop (P = 3e-04);
MVP		0.51
MPC		0.28
ClinPred		0.056	T
GERP RS		2.9
PromoterAI		-0.0034	Neutral
Varity_R		0.16
gMVP		0.27
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs541260898; hg19: chr5-178977721;