rs200353280

Variant names:

• chr12-106687017-C-G
• rs200353280
• NM_213594.3:c.511C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-106687017-C-G
• chr12-106687017-C-T

Variant summary

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

The NM_213594.3(RFX4):​c.511C>G​(p.Arg171Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. R171Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RFX4 NM_213594.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.81
• Publications: 0 publications found

Genes affected

RFX4 (HGNC:9985): (regulatory factor X4) 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, X2, X3, and X5. It has been shown to interact with itself as well as with regulatory factors X2 and X3, but it does not interact with regulatory factor X1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2011]

ENSG00000257545 (HGNC:58967):

LOC100287944 (HGNC:):

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_213594.3. 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
	RFX4	NM_213594.3	MANE Select	c.511C>G	p.Arg171Gly	missense	Exon 6 of 18	NP_998759.1	Q33E94-1
	RFX4	NM_001206691.2		c.538C>G	p.Arg180Gly	missense	Exon 6 of 18	NP_001193620.1	Q33E94-2
	RFX4	NM_032491.6		c.229C>G	p.Arg77Gly	missense	Exon 2 of 14	NP_115880.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX4	ENST00000392842.6	TSL:1 MANE Select	c.511C>G	p.Arg171Gly	missense	Exon 6 of 18	ENSP00000376585.1	Q33E94-1
	RFX4	ENST00000357881.8	TSL:1	c.538C>G	p.Arg180Gly	missense	Exon 6 of 18	ENSP00000350552.4	Q33E94-2
	RFX4	ENST00000229387.6	TSL:1	c.229C>G	p.Arg77Gly	missense	Exon 2 of 14	ENSP00000229387.5	Q33E94-3

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727240

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5764

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.00 AC: 0 AN: 60394

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.95
BayesDel_addAF	Pathogenic	0.32	D
BayesDel_noAF	Pathogenic	0.22
CADD	Uncertain	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.072	T
Eigen	Benign	0.040
Eigen_PC	Benign	0.047
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.95	D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.43	T
MetaSVM	Uncertain	0.012	D
MutationAssessor	Benign	-0.34	N
PhyloP100		3.8
PrimateAI	Pathogenic	0.86	D
PROVEAN	Benign	-1.5	N
REVEL	Uncertain	0.46
Sift	Benign	0.12	T
Sift4G	Benign	0.37	T
Polyphen		0.99	D
Vest4		0.78
MutPred		0.39		Gain of relative solvent accessibility (P = 0.0166)
MVP		0.24
MPC		1.4
ClinPred		0.98	D
GERP RS		1.6
Varity_R		0.25
gMVP		0.90
Mutation Taster		=28/72	disease causing

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: rs200353280; hg19: chr12-107080795;