rs1016489707

Variant names:

• chr5-179596578-C-G
• rs1016489707
• NM_025158.5:c.1528C>G

Your query was ambiguous. Multiple possible variants found:

• chr5-179596578-C-G
• chr5-179596578-C-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.1528C>G​(p.Arg510Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,342 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R510W) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RUFY1 NM_025158.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0530
• 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]

RUFY1-AS1 (HGNC:40903): (RUFY1 antisense RNA 1)

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=0.116158724).

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.1528C>G	p.Arg510Gly	missense	Exon 13 of 18	NP_079434.3
	RUFY1	NM_001040451.3		c.1204C>G	p.Arg402Gly	missense	Exon 12 of 17	NP_001035541.1	Q96T51-2
	RUFY1	NM_001040452.3		c.1204C>G	p.Arg402Gly	missense	Exon 13 of 18	NP_001035542.1	Q96T51-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUFY1	ENST00000319449.9	TSL:1 MANE Select	c.1528C>G	p.Arg510Gly	missense	Exon 13 of 18	ENSP00000325594.4	Q96T51-1
	RUFY1	ENST00000393438.6	TSL:1	c.1204C>G	p.Arg402Gly	missense	Exon 13 of 18	ENSP00000377087.2	Q96T51-2
	RUFY1	ENST00000393448.6	TSL:1	n.*434C>G		non_coding_transcript_exon	Exon 14 of 16	ENSP00000377094.2	J3KPP6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461342 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726992

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52966

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111950

Other (OTH) AF: 0.00 AC: 0 AN: 60382

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.071
BayesDel_addAF	Benign	-0.21	T
BayesDel_noAF	Benign	-0.54
CADD	Benign	13
DANN	Benign	0.96
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.77
Eigen_PC	Benign	-0.90
FATHMM_MKL	Benign	0.14	N
M_CAP	Benign	0.057	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.94	T
MutationAssessor	Benign	1.4	L
PhyloP100		-0.053
PrimateAI	Benign	0.32	T
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.043
Sift	Uncertain	0.0090	D
Sift4G	Benign	0.24	T
Polyphen		0.33	B
Vest4		0.13
MutPred		0.19		Loss of MoRF binding (P = 0.0226)
MVP		0.45
MPC		0.28
ClinPred		0.30	T
GERP RS		-1.4
Varity_R		0.085
gMVP		0.079
Mutation Taster		=100/0	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: rs1016489707; hg19: chr5-179023579;