4-70722593-C-G

Variant names:

• chr4-70722593-C-G
• rs143545853
• NM_001037442.4:c.20C>G

Variant summary

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

The NM_001037442.4(RUFY3):​c.20C>G​(p.Pro7Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts 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. P7L) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: RUFY3 NM_001037442.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.53
• Publications: 0 publications found

Genes affected

RUFY3 (HGNC:30285): (RUN and FYVE domain containing 3) This gene encodes a RPIP8, UNC-14, and NESCA domain-containing protein that is required for maintenance of neuronal polarity. In addition, it has been implicated in mediation of gastric cancer cell migration and invasion via interaction with P21-activated kinase-1, which promotes its expression. The encoded protein localizes to F-actin-enriched invadopodia to induce formation of protrusions, thereby facilitating cell migration. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Sep 2016]

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=0.15318775).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037442.4. 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
	RUFY3	NM_001037442.4	MANE Select	c.20C>G	p.Pro7Arg	missense	Exon 1 of 18	NP_001032519.1	Q7L099-3
	RUFY3	NM_001291994.2		c.20C>G	p.Pro7Arg	missense	Exon 1 of 14	NP_001278923.1
	RUFY3	NM_014961.5		c.20C>G	p.Pro7Arg	missense	Exon 1 of 13	NP_055776.1	Q7L099-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUFY3	ENST00000381006.8	TSL:5 MANE Select	c.20C>G	p.Pro7Arg	missense	Exon 1 of 18	ENSP00000370394.3	Q7L099-3
	RUFY3	ENST00000226328.8	TSL:1	c.20C>G	p.Pro7Arg	missense	Exon 1 of 13	ENSP00000226328.4	Q7L099-1
	RUFY3	ENST00000417478.6	TSL:1	c.358+17299C>G		intron	N/A	ENSP00000399771.2	Q7L099-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.18
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.53
CADD	Uncertain	24
DANN	Uncertain	0.98
DEOGEN2	Benign	0.038	T
Eigen	Benign	-0.0014
Eigen_PC	Benign	0.21
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N
PhyloP100		4.5
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.84	N
REVEL	Benign	0.084
Sift	Benign	0.13	T
Sift4G	Benign	0.34	T
Polyphen		0.51	P
Vest4		0.22
MutPred		0.17		Loss of glycosylation at P7 (P = 0.025)
MVP		0.15
MPC		1.4
ClinPred		0.59	D
GERP RS		5.6
Varity_R		0.16
gMVP		0.64
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: rs143545853; hg19: chr4-71588310;