22-32360572-C-T

Variant names:

• chr22-32360572-C-T
• rs1191639178
• NM_001098535.1:c.694C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001098535.1(RFPL3):​c.694C>T​(p.Pro232Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000205 in 1,461,654 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P232L) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: RFPL3 NM_001098535.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.306
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2515735).

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.694C>T	p.Pro232Ser	missense	Exon 2 of 2	NP_001092005.1	O75679-1
	RFPL3	NM_006604.2		c.607C>T	p.Pro203Ser	missense	Exon 3 of 3	NP_006595.1	O75679-2
	RFPL3S	NR_001450.3		n.542G>A		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.694C>T	p.Pro232Ser	missense	Exon 2 of 2	ENSP00000249007.4	O75679-1
	RFPL3	ENST00000397468.5	TSL:1	c.607C>T	p.Pro203Ser	missense	Exon 3 of 3	ENSP00000380609.1	O75679-2
	RFPL3S	ENST00000382084.10	TSL:1	n.509G>A		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251096 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000205 AC: 3 AN: 1461654 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 727142

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26128

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86248

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111832

Other (OTH) AF: 0.00 AC: 0 AN: 60376

GnomAD4 genome Cov.: 32

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	Uncertain	0.41
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.45
CADD	Benign	15
DANN	Uncertain	0.99
DEOGEN2	Benign	0.080	T
Eigen	Benign	-0.28
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.022	N
LIST_S2	Benign	0.67	T
M_CAP	Benign	0.0033	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.64	T
MutationAssessor	Uncertain	2.4	M
PhyloP100		0.31
PrimateAI	Benign	0.35	T
PROVEAN	Pathogenic	-7.0	D
REVEL	Benign	0.13
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.023	D
Polyphen		1.0	D
Vest4		0.061
MutPred		0.50		Gain of catalytic residue at P232 (P = 0.0329)
MVP		0.66
MPC		0.74
ClinPred		0.69	D
GERP RS		1.4
Varity_R		0.29
gMVP		0.16
Mutation Taster		=98/2	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: rs1191639178; hg19: chr22-32756559;