rs2278134

Variant names:

• chr4-70764444-T-C
• rs2278134
• NM_001037442.4:c.471-31T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037442.4(RUFY3):​c.471-31T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0303 in 1,447,528 control chromosomes in the GnomAD database, including 2,199 homozygotes. 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: 𝑓 0.046 (359 hom., cov: 32)
  • Exomes 𝑓: 0.028 (1840 hom.)
• Consequence: RUFY3 NM_001037442.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.184
• Publications: 7 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: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.194 is higher than 0.05.

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.471-31T>C		intron	N/A	NP_001032519.1
	RUFY3	NM_001291993.2		c.312-31T>C		intron	N/A	NP_001278922.1
	RUFY3	NM_001130709.2		c.651-31T>C		intron	N/A	NP_001124181.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUFY3	ENST00000381006.8	TSL:5 MANE Select	c.471-31T>C		intron	N/A	ENSP00000370394.3
	RUFY3	ENST00000417478.6	TSL:1	c.651-31T>C		intron	N/A	ENSP00000399771.2
	RUFY3	ENST00000226328.8	TSL:1	c.471-31T>C		intron	N/A	ENSP00000226328.4

Frequencies

GnomAD3 genomes AF: 0.0460 AC: 6998 AN: 152132 Hom.: 350 Cov.: 32

Gnomad AFR AF: 0.0833

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.0550

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.00235

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0126

Gnomad OTH AF: 0.0449

GnomAD2 exomes AF: 0.0531 AC: 12975 AN: 244470 AF XY: 0.0521

Gnomad AFR exome AF: 0.0858

Gnomad AMR exome AF: 0.0803

Gnomad ASJ exome AF: 0.0515

Gnomad EAS exome AF: 0.213

Gnomad FIN exome AF: 0.00254

Gnomad NFE exome AF: 0.0137

Gnomad OTH exome AF: 0.0385

GnomAD4 exome AF: 0.0284 AC: 36799 AN: 1295278 Hom.: 1840 Cov.: 18 AF XY: 0.0302 AC XY: 19710 AN XY: 653556

African (AFR) AF: 0.0845 AC: 2508 AN: 29688

American (AMR) AF: 0.0787 AC: 3354 AN: 42634

Ashkenazi Jewish (ASJ) AF: 0.0491 AC: 1215 AN: 24740

East Asian (EAS) AF: 0.213 AC: 8303 AN: 38902

South Asian (SAS) AF: 0.0959 AC: 7820 AN: 81556

European-Finnish (FIN) AF: 0.00323 AC: 171 AN: 52902

Middle Eastern (MID) AF: 0.0382 AC: 206 AN: 5390

European-Non Finnish (NFE) AF: 0.0116 AC: 11168 AN: 964874

Other (OTH) AF: 0.0376 AC: 2054 AN: 54592

GnomAD4 genome AF: 0.0462 AC: 7035 AN: 152250 Hom.: 359 Cov.: 32 AF XY: 0.0481 AC XY: 3580 AN XY: 74438

African (AFR) AF: 0.0840 AC: 3489 AN: 41556

American (AMR) AF: 0.0550 AC: 840 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3470

East Asian (EAS) AF: 0.204 AC: 1054 AN: 5174

South Asian (SAS) AF: 0.102 AC: 492 AN: 4818

European-Finnish (FIN) AF: 0.00235 AC: 25 AN: 10620

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0126 AC: 856 AN: 68006

Other (OTH) AF: 0.0464 AC: 98 AN: 2114

Alfa AF: 0.0263 Hom.: 138

Bravo AF: 0.0509

Asia WGS AF: 0.160 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.54
DANN	Benign	0.68
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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: rs2278134; hg19: chr4-71630161; COSMIC: COSV56911481;