5-179550802-C-G

Variant names:

• chr5-179550802-C-G
• rs1182796142
• NM_025158.5:c.233C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_025158.5(RUFY1):​c.233C>G​(p.Ser78Trp) variant causes a missense change. The variant allele was found at a frequency of 0.0000743 in 1,318,948 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). 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: 𝑓 0.000013 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000082 (0 hom.)
• Consequence: RUFY1 NM_025158.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.69
• 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: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUFY1	NM_025158.5	c.233C>G	p.Ser78Trp	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.233C>G	p.Ser78Trp	missense_variant	Exon 1 of 18	1	NM_025158.5	ENSP00000325594.4
RUFY1	ENST00000393448.6	n.-35C>G		upstream_gene_variant		1		ENSP00000377094.2
RUFY1	ENST00000502984.5	c.-38C>G		upstream_gene_variant		3		ENSP00000425533.1

Frequencies

GnomAD3 genomes AF: 0.0000133 AC: 2 AN: 150358 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: 0.0000296

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000508 AC: 2 AN: 39364 AF XY: 0.0000411

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000121

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000822 AC: 96 AN: 1168590 Hom.: 0 Cov.: 35 AF XY: 0.0000685 AC XY: 39 AN XY: 569590

African (AFR) AF: 0.00 AC: 0 AN: 23724

American (AMR) AF: 0.00 AC: 0 AN: 14396

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17588

East Asian (EAS) AF: 0.00 AC: 0 AN: 25446

South Asian (SAS) AF: 0.00 AC: 0 AN: 45040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 26290

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3462

European-Non Finnish (NFE) AF: 0.0000983 AC: 95 AN: 966186

Other (OTH) AF: 0.0000215 AC: 1 AN: 46458

GnomAD4 genome AF: 0.0000133 AC: 2 AN: 150358 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 73386

African (AFR) AF: 0.00 AC: 0 AN: 41238

American (AMR) AF: 0.00 AC: 0 AN: 15088

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3454

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9814

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.0000296 AC: 2 AN: 67486

Other (OTH) AF: 0.00 AC: 0 AN: 2068

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000151

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 06, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.233C>G (p.S78W) 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 233, causing the serine (S) at amino acid position 78 to be replaced by a tryptophan (W). 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	0.35
BayesDel_addAF	Benign	0.0058	T
BayesDel_noAF	Benign	-0.23
CADD	Uncertain	26
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T
Eigen	Uncertain	0.38
Eigen_PC	Uncertain	0.35
FATHMM_MKL	Uncertain	0.96	D
M_CAP	Pathogenic	0.93	D
MetaRNN	Uncertain	0.65	D
MetaSVM	Benign	-0.57	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.7
PrimateAI	Pathogenic	0.94	D
PROVEAN	Benign	-2.1	N
REVEL	Benign	0.15
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.017	D
Polyphen		0.95	P
Vest4		0.48
MutPred		0.37		Gain of helix (P = 0.0199);
MVP		0.79
MPC		0.64
ClinPred		0.60	D
GERP RS		4.0
PromoterAI		-0.025	Neutral
Varity_R		0.32
gMVP		0.62
Mutation Taster		=79/21	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1182796142; hg19: chr5-178977803;