5-179550633-C-T

Variant names:

• chr5-179550633-C-T
• rs750962218
• NM_025158.5:c.64C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_025158.5(RUFY1):​c.64C>T​(p.Pro22Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000718 in 1,393,506 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: 𝑓 0.0000099 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000070 (0 hom.)
• Consequence: RUFY1 NM_025158.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.139
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.077283084).

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.64C>T	p.Pro22Ser	missense	Exon 1 of 18	NP_079434.3
	LOC128966623	NR_185480.1		n.783+25918C>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.64C>T	p.Pro22Ser	missense	Exon 1 of 18	ENSP00000325594.4	Q96T51-1
	RUFY1	ENST00000891455.1		c.64C>T	p.Pro22Ser	missense	Exon 1 of 19	ENSP00000561514.1
	RUFY1	ENST00000954263.1		c.64C>T	p.Pro22Ser	missense	Exon 1 of 18	ENSP00000624322.1

Frequencies

GnomAD3 genomes AF: 0.00000987 AC: 1 AN: 101278 Hom.: 0 Cov.: 30

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: 0.0000198

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000107 AC: 1 AN: 93374 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000577

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000696 AC: 9 AN: 1292228 Hom.: 0 Cov.: 35 AF XY: 0.00000470 AC XY: 3 AN XY: 638248

African (AFR) AF: 0.00 AC: 0 AN: 26100

American (AMR) AF: 0.0000364 AC: 1 AN: 27440

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21950

East Asian (EAS) AF: 0.00 AC: 0 AN: 26628

South Asian (SAS) AF: 0.00 AC: 0 AN: 70330

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31786

Middle Eastern (MID) AF: 0.000222 AC: 1 AN: 4512

European-Non Finnish (NFE) AF: 0.00000679 AC: 7 AN: 1031178

Other (OTH) AF: 0.00 AC: 0 AN: 52304

GnomAD4 genome AF: 0.00000987 AC: 1 AN: 101278 Hom.: 0 Cov.: 30 AF XY: 0.0000204 AC XY: 1 AN XY: 48968

African (AFR) AF: 0.00 AC: 0 AN: 25340

American (AMR) AF: 0.00 AC: 0 AN: 8526

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2640

East Asian (EAS) AF: 0.00 AC: 0 AN: 2122

South Asian (SAS) AF: 0.00 AC: 0 AN: 2806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 216

European-Non Finnish (NFE) AF: 0.0000198 AC: 1 AN: 50594

Other (OTH) AF: 0.00 AC: 0 AN: 1372

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ExAC AF: 0.0000190 AC: 2

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	0.077
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	9.3
DANN	Benign	0.68
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.12	N
M_CAP	Benign	0.079	D
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.2	L
PhyloP100		0.14
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.020	N
REVEL	Benign	0.079
Sift	Benign	0.087	T
Sift4G	Benign	0.93	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.14		Gain of phosphorylation at P22 (P = 0.0033)
MVP		0.47
MPC		0.22
ClinPred		0.058	T
GERP RS		2.2
PromoterAI		-0.055	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.042
gMVP		0.31
Mutation Taster		=96/4	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: rs750962218; hg19: chr5-178977634; COSMIC: COSV60158464; COSMIC: COSV60158464;