rs79401928

Variant names:

• chr22-29441580-C-T
• rs79401928
• NM_021026.2:c.412C>T

Your query was ambiguous. Multiple possible variants found:

• chr22-29441580-C-T
• chr22-29441580-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_021026.2(RFPL1):​c.412C>T​(p.Leu138Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a pathogenic outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 0)
• Consequence: RFPL1 NM_021026.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.61
• Publications: 1 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: Uncertain_significance. The variant received 2 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.865

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.412C>T	p.Leu138Phe	missense	Exon 2 of 2	NP_066306.2	O75677
	RFPL1	NM_001393612.1		c.325C>T	p.Leu109Phe	missense	Exon 10 of 10	NP_001380541.1
	RFPL1S	NR_002727.2		n.550G>A		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.412C>T	p.Leu138Phe	missense	Exon 2 of 2	ENSP00000346342.2	O75677
	RFPL1S	ENST00000248980.9	TSL:1	n.272-2387G>A		intron	N/A
	RFPL1S	ENST00000461286.4	TSL:4	n.857G>A		non_coding_transcript_exon	Exon 3 of 3

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Cov.: 0

GnomAD4 genome Cov.: 0

Alfa AF: 0.00 Hom.: 0

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	0.28
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	16
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Benign	-0.046
Eigen_PC	Benign	-0.37
FATHMM_MKL	Benign	0.074	N
LIST_S2	Benign	0.82	T
M_CAP	Benign	0.0037	T
MetaRNN	Pathogenic	0.86	D
MetaSVM	Benign	-0.82	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		2.6
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.14
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.010	D
Polyphen		1.0	D
Vest4		0.28
MutPred		0.83		Loss of sheet (P = 0.0817)
MVP		0.58
MPC		0.78
ClinPred		0.99	D
GERP RS		-0.012
Varity_R		0.73
gMVP		0.19
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs79401928; hg19: chr22-29837569; COSMIC: COSV62977306; COSMIC: COSV62977306;