5-179550582-G-C

Variant names:

• chr5-179550582-G-C
• rs1324997610
• NM_025158.5:c.13G>C

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.13G>C​(p.Glu5Gln) variant causes a missense change. The variant allele was found at a frequency of 0.000000931 in 1,074,198 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 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. E5K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 9.3e-7 (0 hom.)
• Consequence: RUFY1 NM_025158.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.29
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13231087).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUFY1	NM_025158.5	c.13G>C	p.Glu5Gln	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.13G>C	p.Glu5Gln	missense_variant	Exon 1 of 18	1	NM_025158.5	ENSP00000325594.4

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 9.31e-7 AC: 1 AN: 1074198 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 525122

African (AFR) AF: 0.00 AC: 0 AN: 21152

American (AMR) AF: 0.00 AC: 0 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16314

East Asian (EAS) AF: 0.00 AC: 0 AN: 22740

South Asian (SAS) AF: 0.00 AC: 0 AN: 45912

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3002

European-Non Finnish (NFE) AF: 0.00000113 AC: 1 AN: 883772

Other (OTH) AF: 0.00 AC: 0 AN: 42152

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	18
DANN	Benign	0.92
DEOGEN2	Benign	0.020	T
Eigen	Benign	-0.41
Eigen_PC	Benign	-0.38
FATHMM_MKL	Uncertain	0.85	D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Benign	0.34	N
PhyloP100		4.3
PrimateAI	Uncertain	0.52	T
PROVEAN	Benign	-0.28	N
REVEL	Benign	0.089
Sift	Benign	0.17	T
Sift4G	Benign	0.096	T
Polyphen		0.079	B
Vest4		0.18
MutPred		0.19		Gain of MoRF binding (P = 0.01);
MVP		0.53
MPC		0.22
ClinPred		0.55	D
GERP RS		3.4
PromoterAI		0.031	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.13
gMVP		0.28
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: rs1324997610; hg19: chr5-178977583;