19-21183324-GAG-AAA

Variant names:

• chr19-21183324-GAG-AAA
• NM_133473.4:c.1021_1023delGAGinsAAA
• ZNF431 p.Glu341Lys

Variant summary

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

The NM_133473.4(ZNF431):​c.1021_1023delGAGinsAAA​(p.Glu341Lys) variant causes a missense change involving the alteration of a non-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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: ZNF431 NM_133473.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.81
• Publications: 0 publications found

Genes affected

ZNF431 (HGNC:20809): (zinc finger protein 431) This gene encodes a member of the Krueppel C2H2-type zinc-finger family of proteins. The encoded protein may negatively regulate transcription of target genes, including the hedgehog signaling pathway receptor patched 1, by interacting with histone deacetylases. Mutations in this gene may be associated with non-syndromic facial clefting in human patients. [provided by RefSeq, Jul 2016]

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_133473.4. 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
	ZNF431	NM_133473.4	MANE Select	c.1021_1023delGAGinsAAA	p.Glu341Lys	missense	N/A	NP_597730.2	Q8TF32
	ZNF431	NM_001319124.2		c.1024_1026delGAGinsAAA	p.Glu342Lys	missense	N/A	NP_001306053.1
	ZNF431	NM_001319126.2		c.748_750delGAGinsAAA	p.Glu250Lys	missense	N/A	NP_001306055.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ZNF431	ENST00000311048.11	TSL:1 MANE Select	c.1021_1023delGAGinsAAA	p.Glu341Lys	missense	N/A	ENSP00000308578.6	Q8TF32
	ZNF431	ENST00000949855.1		c.1144_1146delGAGinsAAA	p.Glu382Lys	missense	N/A	ENSP00000619914.1
	ZNF431	ENST00000949854.1		c.1072_1074delGAGinsAAA	p.Glu358Lys	missense	N/A	ENSP00000619913.1

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.8

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: chr19-21366127;