NM_198483.4:c.501C>T

Variant names:

• chr2-218073357-C-T
• rs747485182
• NM_198483.4:c.501C>T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_198483.4(RUFY4):​c.501C>T​(p.Asp167Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000695 in 1,439,818 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RUFY4 NM_198483.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.29
• Publications: 0 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 -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.074).
• BP7: Synonymous conserved (PhyloP=1.29 with no splicing effect.

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.501C>T	p.Asp167Asp	synonymous	Exon 7 of 13	NP_940885.2	Q6ZNE9-2
	RUFY4	NR_034176.2		n.1880C>T		non_coding_transcript_exon	Exon 8 of 14

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RUFY4	ENST00000697321.1	MANE Select	c.501C>T	p.Asp167Asp	synonymous	Exon 7 of 13	ENSP00000513250.1	Q6ZNE9-2
	RUFY4	ENST00000374155.7	TSL:2	c.501C>T	p.Asp167Asp	synonymous	Exon 6 of 12	ENSP00000363270.3	C9J235
	RUFY4	ENST00000344321.8	TSL:5	c.501C>T	p.Asp167Asp	synonymous	Exon 5 of 11	ENSP00000345900.7	Q6ZNE9-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.95e-7 AC: 1 AN: 1439818 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 713822

African (AFR) AF: 0.00 AC: 0 AN: 33118

American (AMR) AF: 0.00 AC: 0 AN: 41594

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25700

East Asian (EAS) AF: 0.0000258 AC: 1 AN: 38704

South Asian (SAS) AF: 0.00 AC: 0 AN: 82376

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51998

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1101002

Other (OTH) AF: 0.00 AC: 0 AN: 59582

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.10
BayesDel_noAF	Benign	-0.46
CADD	Benign	8.6
DANN	Uncertain	0.98
PhyloP100		1.3
Mutation Taster		=85/15	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: rs747485182; hg19: chr2-218938080;