dbSNP rs2278134: RUFY3:c.471-31T>C (chr4-70764444-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.184

Publications

7 publications found

Variant links:

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]

RUFY3 links:

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ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RUFY3	NM_001037442.4 link	c.471-31T>C		intron_variant	Intron 3 of 17	ENST00000381006.8	NP_001032519.1	Q7L099-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RUFY3	ENST00000381006.8 link	c.471-31T>C		intron_variant	Intron 3 of 17	5	NM_001037442.4	ENSP00000370394.3		Q7L099-3

Frequencies

GnomAD3 genomes

AF:

0.0460

AC:

6998

AN:

152132

Hom.:

350

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0302

AC XY:

19710

AN XY:

653556

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1707

3414

5122

6829

8536

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

622

1244

1866

2488

3110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0462

AC:

7035

AN:

152250

Hom.:

359

Cov.:

AF XY:

0.0481

AC XY:

3580

AN XY:

74438

show subpopulations

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:

AN:

10620

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0126

AC:

856

AN:

68006

Other (OTH)

AF:

0.0464

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

333

666

1000

1333

1666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

180

270

360

450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

0.54

(source)

DANN

Benign

0.68

PhyloP100

0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over