12-106687062-GAT-TAC

Variant names:

• chr12-106687062-GAT-TAC
• NM_213594.3:c.556_558delGATinsTAC
• RFX4 p.Asp186Tyr

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_213594.3(RFX4):​c.556_558delGATinsTAC​(p.Asp186Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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. D186N) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: RFX4 NM_213594.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.56
• 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 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

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.556_558delGATinsTAC	p.Asp186Tyr	missense	N/A	NP_998759.1	Q33E94-1
	RFX4	NM_001206691.2		c.583_585delGATinsTAC	p.Asp195Tyr	missense	N/A	NP_001193620.1	Q33E94-2
	RFX4	NM_032491.6		c.274_276delGATinsTAC	p.Asp92Tyr	missense	N/A	NP_115880.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RFX4	ENST00000392842.6	TSL:1 MANE Select	c.556_558delGATinsTAC	p.Asp186Tyr	missense	N/A	ENSP00000376585.1	Q33E94-1
	RFX4	ENST00000357881.8	TSL:1	c.583_585delGATinsTAC	p.Asp195Tyr	missense	N/A	ENSP00000350552.4	Q33E94-2
	RFX4	ENST00000229387.6	TSL:1	c.274_276delGATinsTAC	p.Asp92Tyr	missense	N/A	ENSP00000229387.5	Q33E94-3

Frequencies

GnomAD3 genomes Cov.: 30

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		9.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr12-107080840;