4-70726177-C-T

Position:

• chr4-70726177-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001037442.4(RUFY3):​c.178+3426C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0988 in 152,070 control chromosomes in the GnomAD database, including 1,596 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 0.099 (1596 hom., cov: 32)
• Consequence: RUFY3 NM_001037442.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RUFY3	NM_001037442.4	c.178+3426C>T		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+3426C>T		intron_variant		5	NM_001037442.4	ENSP00000370394	P1
RUFY3	ENST00000226328.8	c.178+3426C>T		intron_variant		1		ENSP00000226328
RUFY3	ENST00000417478.6	c.358+20883C>T		intron_variant		1		ENSP00000399771
RUFY3	ENST00000503876.5	c.-15+21702C>T		intron_variant		4		ENSP00000426734

Frequencies

GnomAD3 genomes AF: 0.0987 AC: 15000 AN: 151952 Hom.: 1590 Cov.: 32

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.0560

Gnomad AMR AF: 0.0463

Gnomad ASJ AF: 0.0501

Gnomad EAS AF: 0.00154

Gnomad SAS AF: 0.0446

Gnomad FIN AF: 0.0265

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0343

Gnomad OTH AF: 0.0879

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

GnomAD4 genome AF: 0.0988 AC: 15023 AN: 152070 Hom.: 1596 Cov.: 32 AF XY: 0.0964 AC XY: 7170 AN XY: 74346

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.0463

Gnomad4 ASJ AF: 0.0501

Gnomad4 EAS AF: 0.00155

Gnomad4 SAS AF: 0.0438

Gnomad4 FIN AF: 0.0265

Gnomad4 NFE AF: 0.0343

Gnomad4 OTH AF: 0.0870

Alfa AF: 0.0712 Hom.: 143

Bravo AF: 0.109

Asia WGS AF: 0.0330 AC: 117 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.31
DANN	Benign	0.62

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: rs7686646; hg19: chr4-71591894;