rs6815629

Positions:

• chr4-70739674-A-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.78).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.24 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUFY3	NM_001037442.4	c.178+16923A>G		intron_variant		ENST00000381006.8	NP_001032519.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RUFY3	ENST00000381006.8	c.178+16923A>G		intron_variant		5	NM_001037442.4	ENSP00000370394	P1

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

Gnomad4 AFR AF: 0.244

Gnomad4 AMR AF: 0.0437

Gnomad4 ASJ AF: 0.0372

Gnomad4 EAS AF: 0.00154

Gnomad4 SAS AF: 0.0435

Gnomad4 FIN AF: 0.0267

Gnomad4 NFE AF: 0.0340

Gnomad4 OTH AF: 0.0810

Alfa AF: 0.0664 Hom.: 117

Bravo AF: 0.101

Asia WGS AF: 0.0310 AC: 108 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.76
DANN	Benign	0.91

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: rs6815629; hg19: chr4-71605391;