chr4-70775181-A-G

Variant names:

• chr4-70775181-A-G
• rs146855045
• NM_001037442.4:c.772A>G

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001037442.4(RUFY3):​c.772A>G​(p.Thr258Ala) variant causes a missense change. The variant allele was found at a frequency of 0.0000244 in 1,600,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000017 (0 hom.)
• Consequence: RUFY3 NM_001037442.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.41
• 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 -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.28827435).

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.772A>G	p.Thr258Ala	missense	Exon 7 of 18	NP_001032519.1	Q7L099-3
	RUFY3	NM_001291993.2		c.613A>G	p.Thr205Ala	missense	Exon 8 of 19	NP_001278922.1	Q7L099-4
	RUFY3	NM_001130709.2		c.952A>G	p.Thr318Ala	missense	Exon 7 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.772A>G	p.Thr258Ala	missense	Exon 7 of 18	ENSP00000370394.3	Q7L099-3
	RUFY3	ENST00000417478.6	TSL:1	c.952A>G	p.Thr318Ala	missense	Exon 7 of 12	ENSP00000399771.2	Q7L099-2
	RUFY3	ENST00000226328.8	TSL:1	c.772A>G	p.Thr258Ala	missense	Exon 7 of 13	ENSP00000226328.4	Q7L099-1

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152124 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000338

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.0000284 AC: 7 AN: 246580 AF XY: 0.0000225

Gnomad AFR exome AF: 0.000380

Gnomad AMR exome AF: 0.0000302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000166 AC: 24 AN: 1448766 Hom.: 0 Cov.: 27 AF XY: 0.00000555 AC XY: 4 AN XY: 721148

African (AFR) AF: 0.000181 AC: 6 AN: 33064

American (AMR) AF: 0.00 AC: 0 AN: 43932

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25928

East Asian (EAS) AF: 0.00 AC: 0 AN: 39256

South Asian (SAS) AF: 0.00 AC: 0 AN: 84852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53130

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5462

European-Non Finnish (NFE) AF: 0.0000109 AC: 12 AN: 1103424

Other (OTH) AF: 0.000100 AC: 6 AN: 59718

GnomAD4 genome AF: 0.0000986 AC: 15 AN: 152124 Hom.: 0 Cov.: 31 AF XY: 0.000121 AC XY: 9 AN XY: 74316

African (AFR) AF: 0.000338 AC: 14 AN: 41428

American (AMR) AF: 0.00 AC: 0 AN: 15244

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5206

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68036

Other (OTH) AF: 0.000478 AC: 1 AN: 2090

Alfa AF: 0.0000329 Hom.: 0

Bravo AF: 0.0000982

ESP6500AA AF: 0.00114 AC: 5

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000412 AC: 5

ClinVar

ClinVar submissions as Germline

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	0.19
BayesDel_addAF	Benign	-0.041	T
BayesDel_noAF	Uncertain	0.010
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.24	T
Eigen	Uncertain	0.30
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.29	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.3	L
PhyloP100		4.4
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.33
Sift	Benign	0.36	T
Sift4G	Benign	0.20	T
Polyphen		0.074	B
Vest4		0.32
MVP		0.51
MPC		2.1
ClinPred		0.10	T
GERP RS		5.6
Varity_R		0.19
gMVP		0.44
Mutation Taster		=61/39	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: rs146855045; hg19: chr4-71640898;