chr22-32360548-A-G

Variant names:

• chr22-32360548-A-G
• rs61729167
• NM_001098535.1:c.670A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001098535.1(RFPL3):​c.670A>G​(p.Ser224Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000313 in 1,613,790 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00033 (0 hom.)
• Consequence: RFPL3 NM_001098535.1 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.122
• Publications: 1 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.007961154).
• BP6: Variant 22-32360548-A-G is Benign according to our data. Variant chr22-32360548-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2527054.Status of the report is criteria_provided_single_submitter, 1 stars.

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.670A>G	p.Ser224Gly	missense	Exon 2 of 2	NP_001092005.1	O75679-1
	RFPL3	NM_006604.2		c.583A>G	p.Ser195Gly	missense	Exon 3 of 3	NP_006595.1	O75679-2
	RFPL3S	NR_001450.3		n.566T>C		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.670A>G	p.Ser224Gly	missense	Exon 2 of 2	ENSP00000249007.4	O75679-1
	RFPL3	ENST00000397468.5	TSL:1	c.583A>G	p.Ser195Gly	missense	Exon 3 of 3	ENSP00000380609.1	O75679-2
	RFPL3S	ENST00000382084.10	TSL:1	n.533T>C		non_coding_transcript_exon	Exon 4 of 4

Frequencies

GnomAD3 genomes AF: 0.000184 AC: 28 AN: 152132 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000241

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000383 AC: 96 AN: 250664 AF XY: 0.000435

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00109

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000636

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000326 AC: 477 AN: 1461540 Hom.: 0 Cov.: 30 AF XY: 0.000325 AC XY: 236 AN XY: 727092

African (AFR) AF: 0.000299 AC: 10 AN: 33460

American (AMR) AF: 0.0000224 AC: 1 AN: 44712

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26126

East Asian (EAS) AF: 0.000630 AC: 25 AN: 39700

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86242

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53420

Middle Eastern (MID) AF: 0.000521 AC: 3 AN: 5762

European-Non Finnish (NFE) AF: 0.000368 AC: 409 AN: 1111744

Other (OTH) AF: 0.000331 AC: 20 AN: 60374

GnomAD4 genome AF: 0.000184 AC: 28 AN: 152250 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74430

African (AFR) AF: 0.0000241 AC: 1 AN: 41558

American (AMR) AF: 0.000131 AC: 2 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10606

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68010

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000207 Hom.: 0

Bravo AF: 0.000196

ExAC AF: 0.00124 AC: 151

EpiCase AF: 0.000273

EpiControl AF: 0.000474

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.060
BayesDel_addAF	Benign	-0.55	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	0.099
DANN	Benign	0.19
DEOGEN2	Benign	0.0019	T
Eigen	Benign	-1.8
Eigen_PC	Benign	-1.9
FATHMM_MKL	Benign	0.00071	N
LIST_S2	Benign	0.086	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.0080	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.89	N
PhyloP100		-0.12
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.11	N
REVEL	Benign	0.083
Sift	Benign	0.46	T
Sift4G	Benign	0.40	T
Polyphen		0.0	B
Vest4		0.0090
MVP		0.27
MPC		0.17
ClinPred		0.0094	T
GERP RS		-2.7
Varity_R		0.029
gMVP		0.030
Mutation Taster		=99/1	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: rs61729167; hg19: chr22-32756535; COSMIC: COSV50750827; COSMIC: COSV50750827;