NM_001037442.4:c.764dupG

Variant names:

• chr4-70775171-C-CG
• rs869312879
• NM_001037442.4:c.764dupG

Variant summary

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

The NM_001037442.4(RUFY3):​c.764dupG​(p.Gln256SerfsTer39) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 31)
• Consequence: RUFY3 NM_001037442.4 frameshift
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.03
• 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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.764dupG	p.Gln256SerfsTer39	frameshift	Exon 7 of 18	NP_001032519.1	Q7L099-3
	RUFY3	NM_001291993.2		c.605dupG	p.Gln203SerfsTer39	frameshift	Exon 8 of 19	NP_001278922.1	Q7L099-4
	RUFY3	NM_001130709.2		c.944dupG	p.Gln316SerfsTer39	frameshift	Exon 7 of 12	NP_001124181.1	Q7L099-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUFY3	ENST00000381006.8	TSL:5 MANE Select	c.764dupG	p.Gln256SerfsTer39	frameshift	Exon 7 of 18	ENSP00000370394.3	Q7L099-3
	RUFY3	ENST00000417478.6	TSL:1	c.944dupG	p.Gln316SerfsTer39	frameshift	Exon 7 of 12	ENSP00000399771.2	Q7L099-2
	RUFY3	ENST00000226328.8	TSL:1	c.764dupG	p.Gln256SerfsTer39	frameshift	Exon 7 of 13	ENSP00000226328.4	Q7L099-1

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 27

GnomAD4 genome Cov.: 31

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
PhyloP100		8.0

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: rs869312879; hg19: chr4-71640888;