rs769353990

Variant names:

• chr19-5994869-C-A
• rs769353990
• NM_000635.4:c.2138G>T

Your query was ambiguous. Multiple possible variants found:

• chr19-5994869-C-A
• chr19-5994869-C-T

Variant summary

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

The NM_000635.4(RFX2):​c.2138G>T​(p.Arg713Leu) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,458,090 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R713H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: RFX2 NM_000635.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.95
• Publications: 0 publications found

Genes affected

RFX2 (HGNC:9983): (regulatory factor X2) This gene is a member of the regulatory factor X gene family, which encodes transcription factors that contain a highly-conserved winged helix DNA binding domain. The protein encoded by this gene is structurally related to regulatory factors X1, X3, X4, and X5. It is a transcriptional activator that can bind DNA as a monomer or as a heterodimer with other RFX family members. This protein can bind to cis elements in the promoter of the IL-5 receptor alpha gene. Two transcript variants encoding different isoforms have been described for this gene, and both variants utilize alternative polyadenylation sites. [provided by RefSeq, Jul 2008]

RANBP3-DT (HGNC:55312): (RANBP3 divergent transcript)

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=0.12164298).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000635.4. 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
	RFX2	NM_000635.4	MANE Select	c.2138G>T	p.Arg713Leu	missense	Exon 18 of 18	NP_000626.2
	RFX2	NM_134433.3		c.2063G>T	p.Arg688Leu	missense	Exon 17 of 17	NP_602309.1	P48378-2
	RANBP3-DT	NR_046376.1		n.112+16355C>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX2	ENST00000303657.10	TSL:1 MANE Select	c.2138G>T	p.Arg713Leu	missense	Exon 18 of 18	ENSP00000306335.4	P48378-1
	RFX2	ENST00000359161.7	TSL:1	c.2138G>T	p.Arg713Leu	missense	Exon 18 of 18	ENSP00000352076.3	P48378-1
	RFX2	ENST00000926861.1		c.2159G>T	p.Arg720Leu	missense	Exon 18 of 18	ENSP00000596920.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1458090 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 725710

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26114

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86238

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50012

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5754

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111770

Other (OTH) AF: 0.00 AC: 0 AN: 60340

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.24	T
Eigen	Benign	0.14
Eigen_PC	Uncertain	0.24
FATHMM_MKL	Uncertain	0.80	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.081	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.50	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		4.9
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-2.7	D
REVEL	Benign	0.20
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.010	D
Polyphen		0.064	B
Vest4		0.38
MutPred		0.15		Loss of glycosylation at P716 (P = 0.0735)
MVP		0.11
MPC		1.8
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.41
gMVP		0.73
Mutation Taster		=73/27	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs769353990; hg19: chr19-5994880;