NM_001037442.4:c.20C>G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. Variant got 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.

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

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.15318775).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUFY3	NM_001037442.4	c.20C>G	p.Pro7Arg	missense_variant	Exon 1 of 18	ENST00000381006.8	NP_001032519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUFY3	ENST00000381006.8	c.20C>G	p.Pro7Arg	missense_variant	Exon 1 of 18	5	NM_001037442.4	ENSP00000370394.3
RUFY3	ENST00000226328.8	c.20C>G	p.Pro7Arg	missense_variant	Exon 1 of 13	1		ENSP00000226328.4
RUFY3	ENST00000417478.6	c.358+17299C>G		intron_variant	Intron 1 of 11	1		ENSP00000399771.2
RUFY3	ENST00000503876.5	c.-15+18118C>G		intron_variant	Intron 1 of 4	4		ENSP00000426734.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.15	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-0.84	N;N
REVEL	Benign	0.084
Sift	Benign	0.13	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.51	P;B
Vest4		0.22
MutPred		0.17		Loss of glycosylation at P7 (P = 0.025);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

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr4-71588310;