11-125429997-ATG-GTC

Variant names:

• chr11-125429997-ATG-GTC
• NM_001382323.2:c.1048_1050delATGinsGTC
• PKNOX2 p.Met350Val

Variant summary

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

The NM_001382323.2(PKNOX2):​c.1048_1050delATGinsGTC​(p.Met350Val) 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 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: PKNOX2 NM_001382323.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.91
• Publications: 0 publications found

Genes affected

PKNOX2 (HGNC:16714): (PBX/knotted 1 homeobox 2) Homeodomain proteins are sequence-specific transcription factors that share a highly conserved DNA-binding domain and play fundamental roles in cell proliferation, differentiation, and death. PKNOX2 belongs to the TALE (3-amino acid loop extension) class of homeodomain proteins characterized by a 3-amino acid extension between alpha helices 1 and 2 within the homeodomain (Imoto et al., 2001 [PubMed 11549286]).[supplied by OMIM, Oct 2009]

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_001382323.2. 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
	PKNOX2	NM_001382323.2	MANE Select	c.1048_1050delATGinsGTC	p.Met350Val	missense	N/A	NP_001369252.1	Q96KN3-1
	PKNOX2	NM_001382324.1		c.1048_1050delATGinsGTC	p.Met350Val	missense	N/A	NP_001369253.1	Q96KN3-1
	PKNOX2	NM_001382325.1		c.1048_1050delATGinsGTC	p.Met350Val	missense	N/A	NP_001369254.1	Q96KN3-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKNOX2	ENST00000298282.14	TSL:1 MANE Select	c.1048_1050delATGinsGTC	p.Met350Val	missense	N/A	ENSP00000298282.8	Q96KN3-1
	PKNOX2	ENST00000526955.1	TSL:1	n.2163_2165delATGinsGTC		non_coding_transcript_exon	Exon 5 of 6
	PKNOX2	ENST00000878499.1		c.1216_1218delATGinsGTC	p.Met406Val	missense	N/A	ENSP00000548558.1

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		9.9

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: chr11-125299893;