rs116225803

Variant names:

• chr4-70773581-A-G
• rs116225803
• NM_001037442.4:c.758+9A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001037442.4(RUFY3):​c.758+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00148 in 1,596,388 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0081 (15 hom., cov: 32)
  • Exomes 𝑓: 0.00078 (8 hom.)
• Consequence: RUFY3 NM_001037442.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.68
• Publications: 1 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 4-70773581-A-G is Benign according to our data. Variant chr4-70773581-A-G is described in ClinVar as Benign. ClinVar VariationId is 720186.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00814 (1240/152332) while in subpopulation AFR AF = 0.0284 (1179/41580). AF 95% confidence interval is 0.027. There are 15 homozygotes in GnomAd4. There are 587 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 15 AR gene

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.758+9A>G		intron	N/A	NP_001032519.1	Q7L099-3
	RUFY3	NM_001291993.2		c.599+9A>G		intron	N/A	NP_001278922.1	Q7L099-4
	RUFY3	NM_001130709.2		c.938+9A>G		intron	N/A	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.758+9A>G		intron	N/A	ENSP00000370394.3	Q7L099-3
	RUFY3	ENST00000417478.6	TSL:1	c.938+9A>G		intron	N/A	ENSP00000399771.2	Q7L099-2
	RUFY3	ENST00000226328.8	TSL:1	c.758+9A>G		intron	N/A	ENSP00000226328.4	Q7L099-1

Frequencies

GnomAD3 genomes AF: 0.00815 AC: 1240 AN: 152214 Hom.: 15 Cov.: 32

Gnomad AFR AF: 0.0284

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.00573

GnomAD2 exomes AF: 0.00211 AC: 515 AN: 244644 AF XY: 0.00169

Gnomad AFR exome AF: 0.0293

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000358

Gnomad OTH exome AF: 0.000845

GnomAD4 exome AF: 0.000776 AC: 1120 AN: 1444056 Hom.: 8 Cov.: 26 AF XY: 0.000681 AC XY: 490 AN XY: 719374

African (AFR) AF: 0.0286 AC: 943 AN: 32990

American (AMR) AF: 0.00124 AC: 55 AN: 44320

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25930

East Asian (EAS) AF: 0.00 AC: 0 AN: 39460

South Asian (SAS) AF: 0.0000235 AC: 2 AN: 85006

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53288

Middle Eastern (MID) AF: 0.000700 AC: 4 AN: 5718

European-Non Finnish (NFE) AF: 0.0000191 AC: 21 AN: 1097608

Other (OTH) AF: 0.00159 AC: 95 AN: 59736

GnomAD4 genome AF: 0.00814 AC: 1240 AN: 152332 Hom.: 15 Cov.: 32 AF XY: 0.00788 AC XY: 587 AN XY: 74492

African (AFR) AF: 0.0284 AC: 1179 AN: 41580

American (AMR) AF: 0.00248 AC: 38 AN: 15300

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000118 AC: 8 AN: 68026

Other (OTH) AF: 0.00567 AC: 12 AN: 2116

Alfa AF: 0.00406 Hom.: 6

Bravo AF: 0.00917

Asia WGS AF: 0.00144 AC: 5 AN: 3476

ClinVar

ClinVar submissions as Germline

Significance: 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	-0.83
CADD	Benign	6.8
DANN	Benign	0.47
PhyloP100		1.7
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs116225803; hg19: chr4-71639298;