NM_021026.2:c.466C>A

Variant names:

• chr22-29441634-C-A
• rs757533010
• NM_021026.2:c.466C>A

Variant summary

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

The NM_021026.2(RFPL1):​c.466C>A​(p.Arg156Arg) 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: 31)
• Consequence: RFPL1 NM_021026.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.571
• Publications: 0 publications found

Genes affected

RFPL1 (HGNC:9977): (ret finger protein like 1) Predicted to enable ubiquitin-protein transferase activity. Involved in several processes, including negative regulation of G2/M transition of mitotic cell cycle; negative regulation of cell division; and positive regulation of proteolysis. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RFPL1S (HGNC:9978): (RFPL1 antisense RNA 1)

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=-0.75).
• BP7: Synonymous conserved (PhyloP=0.571 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021026.2. 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
	RFPL1	NM_021026.2	MANE Select	c.466C>A	p.Arg156Arg	synonymous	Exon 2 of 2	NP_066306.2	O75677
	RFPL1	NM_001393612.1		c.379C>A	p.Arg127Arg	synonymous	Exon 10 of 10	NP_001380541.1
	RFPL1S	NR_002727.2		n.496G>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFPL1	ENST00000354373.2	TSL:1 MANE Select	c.466C>A	p.Arg156Arg	synonymous	Exon 2 of 2	ENSP00000346342.2	O75677
	RFPL1S	ENST00000248980.9	TSL:1	n.272-2441G>T		intron	N/A
	RFPL1S	ENST00000461286.4	TSL:4	n.803G>T		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.86
DANN	Benign	0.59
PhyloP100		0.57

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: rs757533010; hg19: chr22-29837623;