22-32358080-G-A

Variant names:

• chr22-32358080-G-A
• rs148000561
• NM_001098535.1:c.9G>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_001098535.1(RFPL3):​c.9G>A​(p.Arg3Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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)
• Consequence: RFPL3 NM_001098535.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.29
• Publications: 0 publications found

Genes affected

RFPL3 (HGNC:9980): (ret finger protein like 3) Predicted to enable ubiquitin-protein transferase activity. Predicted to be involved in positive regulation of transcription, DNA-templated. Predicted to be located in cytoplasm. Predicted to be active in chromatin and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP7: Synonymous conserved (PhyloP=-1.29 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001098535.1. 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
	RFPL3	NM_001098535.1	MANE Select	c.9G>A	p.Arg3Arg	synonymous	Exon 1 of 2	NP_001092005.1	O75679-1
	RFPL3	NM_006604.2		c.-5-74G>A		intron	N/A	NP_006595.1	O75679-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFPL3	ENST00000249007.4	TSL:1 MANE Select	c.9G>A	p.Arg3Arg	synonymous	Exon 1 of 2	ENSP00000249007.4	O75679-1
	RFPL3	ENST00000397468.5	TSL:1	c.-5-74G>A		intron	N/A	ENSP00000380609.1	O75679-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.96
DANN	Benign	0.67
PhyloP100		-1.3
PromoterAI		0.0030	Neutral

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: rs148000561; hg19: chr22-32754067; COSMIC: COSV50748086; COSMIC: COSV50748086;