5-179550639-C-T

Variant names:

• chr5-179550639-C-T
• NM_025158.5:c.70C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_025158.5(RUFY1):​c.70C>T​(p.Pro24Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000232 in 1,293,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 27)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: RUFY1 NM_025158.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.337
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04767999).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_025158.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUFY1	NM_025158.5	MANE Select	c.70C>T	p.Pro24Ser	missense	Exon 1 of 18	NP_079434.3
	LOC128966623	NR_185480.1		n.783+25924C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUFY1	ENST00000319449.9	TSL:1 MANE Select	c.70C>T	p.Pro24Ser	missense	Exon 1 of 18	ENSP00000325594.4	Q96T51-1
	RUFY1	ENST00000891455.1		c.70C>T	p.Pro24Ser	missense	Exon 1 of 19	ENSP00000561514.1
	RUFY1	ENST00000954263.1		c.70C>T	p.Pro24Ser	missense	Exon 1 of 18	ENSP00000624322.1

Frequencies

GnomAD3 genomes Cov.: 27

GnomAD4 exome AF: 0.00000232 AC: 3 AN: 1293004 Hom.: 0 Cov.: 35 AF XY: 0.00000313 AC XY: 2 AN XY: 639030

African (AFR) AF: 0.00 AC: 0 AN: 25838

American (AMR) AF: 0.00 AC: 0 AN: 27890

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21954

East Asian (EAS) AF: 0.00 AC: 0 AN: 26594

South Asian (SAS) AF: 0.00 AC: 0 AN: 70892

European-Finnish (FIN) AF: 0.0000633 AC: 2 AN: 31572

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4590

European-Non Finnish (NFE) AF: 9.69e-7 AC: 1 AN: 1031490

Other (OTH) AF: 0.00 AC: 0 AN: 52184

GnomAD4 genome Cov.: 27

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	5.4
DANN	Benign	0.69
DEOGEN2	Benign	0.020	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.15	N
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.060	N
PhyloP100		-0.34
PrimateAI	Benign	0.48	T
PROVEAN	Benign	-0.22	N
REVEL	Benign	0.030
Sift	Benign	0.81	T
Sift4G	Benign	0.72	T
Polyphen		0.0	B
Vest4		0.11
MutPred		0.22		Gain of phosphorylation at P24 (P = 0.0022)
MVP		0.30
MPC		0.22
ClinPred		0.040	T
GERP RS		-0.94
PromoterAI		-0.064	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.029
gMVP		0.34
Mutation Taster		=99/1	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

hg19: chr5-178977640;