chr22-32360318-T-C

Variant names:

• chr22-32360318-T-C
• NM_001098535.1:c.440T>C

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001098535.1(RFPL3):​c.440T>C​(p.Val147Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: RFPL3 NM_001098535.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.91
• 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]

RFPL3S (HGNC:9981): (RFPL3 antisense)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

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.440T>C	p.Val147Ala	missense	Exon 2 of 2	NP_001092005.1	O75679-1
	RFPL3	NM_006604.2		c.353T>C	p.Val118Ala	missense	Exon 3 of 3	NP_006595.1	O75679-2
	RFPL3S	NR_001450.3		n.796A>G		non_coding_transcript_exon	Exon 4 of 4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFPL3	ENST00000249007.4	TSL:1 MANE Select	c.440T>C	p.Val147Ala	missense	Exon 2 of 2	ENSP00000249007.4	O75679-1
	RFPL3	ENST00000397468.5	TSL:1	c.353T>C	p.Val118Ala	missense	Exon 3 of 3	ENSP00000380609.1	O75679-2
	RFPL3S	ENST00000382084.10	TSL:1	n.763A>G		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

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	0.32
BayesDel_addAF	Benign	-0.0044	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.92
DEOGEN2	Benign	0.14	T
Eigen	Benign	-0.070
Eigen_PC	Benign	-0.36
FATHMM_MKL	Benign	0.67	D
LIST_S2	Benign	0.47	T
M_CAP	Benign	0.0023	T
MetaRNN	Uncertain	0.45	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		1.9
PrimateAI	Uncertain	0.52	T
PROVEAN	Uncertain	-3.8	D
REVEL	Benign	0.18
Sift	Uncertain	0.0030	D
Sift4G	Benign	0.18	T
Polyphen		1.0	D
Vest4		0.25
MutPred		0.74		Loss of stability (P = 0.0111)
MVP		0.33
MPC		0.62
ClinPred		0.57	D
GERP RS		0.66
Varity_R		0.19
gMVP		0.26
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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

hg19: chr22-32756305;