rs6815629

Variant names:

• chr4-70739674-A-G
• rs6815629
• NM_001037442.4:c.178+16923A>G

Variant summary

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

The NM_001037442.4(RUFY3):​c.178+16923A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0919 in 152,136 control chromosomes in the GnomAD database, including 1,379 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 0.092 (1379 hom., cov: 31)
• Consequence: RUFY3 NM_001037442.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.186
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 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.178+16923A>G		intron	N/A	NP_001032519.1	Q7L099-3
	RUFY3	NM_001291993.2		c.-35-1953A>G		intron	N/A	NP_001278922.1	Q7L099-4
	RUFY3	NM_001130709.2		c.359-22845A>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.178+16923A>G		intron	N/A	ENSP00000370394.3	Q7L099-3
	RUFY3	ENST00000417478.6	TSL:1	c.359-22845A>G		intron	N/A	ENSP00000399771.2	Q7L099-2
	RUFY3	ENST00000226328.8	TSL:1	c.178+16923A>G		intron	N/A	ENSP00000226328.4	Q7L099-1

Frequencies

GnomAD3 genomes AF: 0.0918 AC: 13960 AN: 152018 Hom.: 1375 Cov.: 31

Gnomad AFR AF: 0.244

Gnomad AMI AF: 0.0559

Gnomad AMR AF: 0.0437

Gnomad ASJ AF: 0.0372

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0443

Gnomad FIN AF: 0.0267

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0340

Gnomad OTH AF: 0.0818

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0919 AC: 13975 AN: 152136 Hom.: 1379 Cov.: 31 AF XY: 0.0892 AC XY: 6637 AN XY: 74392

African (AFR) AF: 0.244 AC: 10116 AN: 41446

American (AMR) AF: 0.0437 AC: 667 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0372 AC: 129 AN: 3470

East Asian (EAS) AF: 0.00154 AC: 8 AN: 5184

South Asian (SAS) AF: 0.0435 AC: 210 AN: 4824

European-Finnish (FIN) AF: 0.0267 AC: 283 AN: 10612

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0340 AC: 2311 AN: 68004

Other (OTH) AF: 0.0810 AC: 171 AN: 2112

Alfa AF: 0.0715 Hom.: 137

Bravo AF: 0.101

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.76
DANN	Benign	0.91
PhyloP100		-0.19
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: rs6815629; hg19: chr4-71605391;