rs2278134

Positions:

• chr4-70764444-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RUFY3	NM_001037442.4	c.471-31T>C		intron_variant		ENST00000381006.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RUFY3	ENST00000381006.8	c.471-31T>C		intron_variant		5	NM_001037442.4	P1

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

GnomAD3 exomes AF: 0.0531 AC: 12975 AN: 244470 Hom.: 787 AF XY: 0.0521 AC XY: 6883 AN XY: 132172

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 SAS exome AF: 0.0975

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

Gnomad4 AFR exome AF: 0.0845

Gnomad4 AMR exome AF: 0.0787

Gnomad4 ASJ exome AF: 0.0491

Gnomad4 EAS exome AF: 0.213

Gnomad4 SAS exome AF: 0.0959

Gnomad4 FIN exome AF: 0.00323

Gnomad4 NFE exome AF: 0.0116

Gnomad4 OTH exome AF: 0.0376

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

Gnomad4 AFR AF: 0.0840

Gnomad4 AMR AF: 0.0550

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.204

Gnomad4 SAS AF: 0.102

Gnomad4 FIN AF: 0.00235

Gnomad4 NFE AF: 0.0126

Gnomad4 OTH AF: 0.0464

Alfa AF: 0.0231 Hom.: 78

Bravo AF: 0.0509

Asia WGS AF: 0.160 AC: 555 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.54
DANN	Benign	0.68

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

Publications

LitVar

Other links and lift over

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