chr4-70763628-C-T

Variant names:

• chr4-70763628-C-T
• rs139284262
• NM_001037442.4:c.429C>T

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Moderate BP6_Moderate BP7

The NM_001037442.4(RUFY3):​c.429C>T​(p.Ala143Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000149 in 1,611,878 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000059 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000010 (0 hom.)
• Consequence: RUFY3 NM_001037442.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.214
• Publications: 2 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: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 4-70763628-C-T is Benign according to our data. Variant chr4-70763628-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 735511.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.214 with no splicing effect.

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.429C>T	p.Ala143Ala	synonymous	Exon 3 of 18	NP_001032519.1	Q7L099-3
	RUFY3	NM_001291993.2		c.270C>T	p.Ala90Ala	synonymous	Exon 4 of 19	NP_001278922.1	Q7L099-4
	RUFY3	NM_001130709.2		c.609C>T	p.Ala203Ala	synonymous	Exon 3 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.429C>T	p.Ala143Ala	synonymous	Exon 3 of 18	ENSP00000370394.3	Q7L099-3
	RUFY3	ENST00000417478.6	TSL:1	c.609C>T	p.Ala203Ala	synonymous	Exon 3 of 12	ENSP00000399771.2	Q7L099-2
	RUFY3	ENST00000226328.8	TSL:1	c.429C>T	p.Ala143Ala	synonymous	Exon 3 of 13	ENSP00000226328.4	Q7L099-1

Frequencies

GnomAD3 genomes AF: 0.0000592 AC: 9 AN: 152046 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000121 AC: 3 AN: 247932 AF XY: 0.00000744

Gnomad AFR exome AF: 0.000126

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000901

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000103 AC: 15 AN: 1459714 Hom.: 0 Cov.: 29 AF XY: 0.00000826 AC XY: 6 AN XY: 726304

African (AFR) AF: 0.000209 AC: 7 AN: 33442

American (AMR) AF: 0.00 AC: 0 AN: 44652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26112

East Asian (EAS) AF: 0.00 AC: 0 AN: 39644

South Asian (SAS) AF: 0.00 AC: 0 AN: 86114

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53402

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5596

European-Non Finnish (NFE) AF: 0.00000540 AC: 6 AN: 1110436

Other (OTH) AF: 0.0000332 AC: 2 AN: 60316

GnomAD4 genome AF: 0.0000591 AC: 9 AN: 152164 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74396

African (AFR) AF: 0.000217 AC: 9 AN: 41498

American (AMR) AF: 0.00 AC: 0 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10592

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2110

Alfa AF: 0.000112 Hom.: 0

Bravo AF: 0.000117

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	11
DANN	Benign	0.68
PhyloP100		-0.21

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: rs139284262; hg19: chr4-71629345;