NM_001037442.4:c.969A>G

Variant names:

• chr4-70783165-A-G
• rs755827378
• NM_001037442.4:c.969A>G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001037442.4(RUFY3):​c.969A>G​(p.Ile323Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000106 in 1,599,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000026 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000090 (0 hom.)
• Consequence: RUFY3 NM_001037442.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.71
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.030346036).

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.969A>G	p.Ile323Met	missense	Exon 9 of 18	NP_001032519.1	Q7L099-3
	RUFY3	NM_001291993.2		c.810A>G	p.Ile270Met	missense	Exon 10 of 19	NP_001278922.1	Q7L099-4
	RUFY3	NM_001130709.2		c.1149A>G	p.Ile383Met	missense	Exon 9 of 12	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.969A>G	p.Ile323Met	missense	Exon 9 of 18	ENSP00000370394.3	Q7L099-3
	RUFY3	ENST00000417478.6	TSL:1	c.1149A>G	p.Ile383Met	missense	Exon 9 of 12	ENSP00000399771.2	Q7L099-2
	RUFY3	ENST00000226328.8	TSL:1	c.969A>G	p.Ile323Met	missense	Exon 9 of 13	ENSP00000226328.4	Q7L099-1

Frequencies

GnomAD3 genomes AF: 0.0000263 AC: 4 AN: 152256 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000441 AC: 11 AN: 249352 AF XY: 0.0000445

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000602

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000899 AC: 13 AN: 1446838 Hom.: 0 Cov.: 26 AF XY: 0.00000694 AC XY: 5 AN XY: 720656

African (AFR) AF: 0.00 AC: 0 AN: 33148

American (AMR) AF: 0.00 AC: 0 AN: 44474

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.000303 AC: 12 AN: 39578

South Asian (SAS) AF: 0.00 AC: 0 AN: 85746

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53388

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5718

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1098838

Other (OTH) AF: 0.0000167 AC: 1 AN: 59920

GnomAD4 genome AF: 0.0000263 AC: 4 AN: 152256 Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3 AN XY: 74394

African (AFR) AF: 0.00 AC: 0 AN: 41482

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.000770 AC: 4 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4838

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000332 Hom.: 0

Bravo AF: 0.0000340

ExAC AF: 0.0000247 AC: 3

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.073	T
Eigen	Benign	0.051
Eigen_PC	Benign	0.17
FATHMM_MKL	Uncertain	0.77	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.0069	T
MetaRNN	Benign	0.030	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		1.7
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.2	N
REVEL	Benign	0.025
Sift	Benign	0.072	T
Sift4G	Benign	0.14	T
Polyphen		0.17	B
Vest4		0.25
MutPred		0.17		Gain of glycosylation at Y322 (P = 0.0012)
MVP		0.14
MPC		1.3
ClinPred		0.15	T
GERP RS		4.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Varity_R		0.063
gMVP		0.15
Mutation Taster		=97/3	polymorphism

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: rs755827378; hg19: chr4-71648882;