chr2-218072449-C-T

Variant names:

• chr2-218072449-C-T
• rs1436025590
• NM_198483.4:c.229C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_198483.4(RUFY4):​c.229C>T​(p.Arg77Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000131 in 1,537,254 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00014 (0 hom.)
• Consequence: RUFY4 NM_198483.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.610
• Publications: 1 publications found

Genes affected

RUFY4 (HGNC:24804): (RUN and FYVE domain containing 4) Enables phosphatidylinositol-3-phosphate binding activity. Involved in autophagosome assembly; cellular response to interleukin-4; and positive regulation of macroautophagy. Located in autophagosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.21086171).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198483.4. 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
	RUFY4	NM_198483.4	MANE Select	c.229C>T	p.Arg77Trp	missense	Exon 5 of 13	NP_940885.2	Q6ZNE9-2
	RUFY4	NR_034176.2		n.1715C>T		non_coding_transcript_exon	Exon 7 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUFY4	ENST00000697321.1	MANE Select	c.229C>T	p.Arg77Trp	missense	Exon 5 of 13	ENSP00000513250.1	Q6ZNE9-2
	RUFY4	ENST00000374155.7	TSL:2	c.229C>T	p.Arg77Trp	missense	Exon 4 of 12	ENSP00000363270.3	C9J235
	RUFY4	ENST00000344321.8	TSL:5	c.229C>T	p.Arg77Trp	missense	Exon 3 of 11	ENSP00000345900.7	Q6ZNE9-2

Frequencies

GnomAD3 genomes AF: 0.0000920 AC: 14 AN: 152224 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000720

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: 0.0000441

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000351 AC: 5 AN: 142314 AF XY: 0.0000525

Gnomad AFR exome AF: 0.000130

Gnomad AMR exome AF: 0.0000407

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000351

Gnomad OTH exome AF: 0.000234

GnomAD4 exome AF: 0.000136 AC: 188 AN: 1385030 Hom.: 0 Cov.: 31 AF XY: 0.000129 AC XY: 88 AN XY: 683454

African (AFR) AF: 0.0000317 AC: 1 AN: 31590

American (AMR) AF: 0.0000280 AC: 1 AN: 35696

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35864

South Asian (SAS) AF: 0.0000379 AC: 3 AN: 79224

European-Finnish (FIN) AF: 0.0000285 AC: 1 AN: 35030

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5628

European-Non Finnish (NFE) AF: 0.000166 AC: 179 AN: 1078888

Other (OTH) AF: 0.0000518 AC: 3 AN: 57928

GnomAD4 genome AF: 0.0000920 AC: 14 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.0000941 AC XY: 7 AN XY: 74372

African (AFR) AF: 0.00 AC: 0 AN: 41454

American (AMR) AF: 0.000720 AC: 11 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5202

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

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

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68036

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

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.000125

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	0.11
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.049	T
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.48
FATHMM_MKL	Benign	0.092	N
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.026	D
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		0.61
PrimateAI	Benign	0.22	T
PROVEAN	Pathogenic	-5.0	D
REVEL	Benign	0.065
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0020	D
Vest4		0.34
MutPred		0.61		Gain of catalytic residue at L75 (P = 0.0044)
MVP		0.52
MPC		0.20
ClinPred		0.76	D
GERP RS		2.9
Varity_R		0.26
gMVP		0.37
Mutation Taster		=95/5	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: rs1436025590; hg19: chr2-218937172; COSMIC: COSV100723055; COSMIC: COSV100723055;