rs746465399

Variant names:

• chr12-106639356-C-G
• rs746465399
• NM_213594.3:c.155C>G

Your query was ambiguous. Multiple possible variants found:

• chr12-106639356-C-G
• chr12-106639356-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_213594.3(RFX4):​c.155C>G​(p.Ala52Gly) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,388 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. A52V) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: RFX4 NM_213594.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.49
• 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:):

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.34636414).

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.155C>G	p.Ala52Gly	missense	Exon 3 of 18	NP_998759.1	Q33E94-1
	RFX4	NM_001206691.2		c.182C>G	p.Ala61Gly	missense	Exon 3 of 18	NP_001193620.1	Q33E94-2
	LOC100287944	NR_040246.1		n.143-131546G>C		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX4	ENST00000392842.6	TSL:1 MANE Select	c.155C>G	p.Ala52Gly	missense	Exon 3 of 18	ENSP00000376585.1	Q33E94-1
	RFX4	ENST00000357881.8	TSL:1	c.182C>G	p.Ala61Gly	missense	Exon 3 of 18	ENSP00000350552.4	Q33E94-2
	RFX4	ENST00000536688.5	TSL:1	n.287C>G		non_coding_transcript_exon	Exon 3 of 15

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461388 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726970

African (AFR) AF: 0.00 AC: 0 AN: 33462

American (AMR) AF: 0.00 AC: 0 AN: 44676

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.00 AC: 0 AN: 86168

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53392

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111774

Other (OTH) AF: 0.00 AC: 0 AN: 60372

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	0.00036	T
BayesDel_noAF	Benign	-0.24
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.084	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.52
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.93	D
M_CAP	Benign	0.029	D
MetaRNN	Benign	0.35	T
MetaSVM	Benign	-0.71	T
MutationAssessor	Benign	0.0	N
PhyloP100		5.5
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.21
Sift	Benign	0.094	T
Sift4G	Benign	0.29	T
Polyphen		0.98	D
Vest4		0.49
MutPred		0.30		Loss of stability (P = 0.0618)
MVP		0.043
MPC		0.87
ClinPred		0.96	D
GERP RS		5.3
Varity_R		0.23
gMVP		0.54
Mutation Taster		=52/48	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: rs746465399; hg19: chr12-107033134;