11-125367898-C-T

Variant names:

• chr11-125367898-C-T
• rs1295459678
• NM_001382323.2:c.140C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001382323.2(PKNOX2):​c.140C>T​(p.Ala47Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict 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. A47D) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: PKNOX2 NM_001382323.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.14
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16123903).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PKNOX2	NM_001382323.2	c.140C>T	p.Ala47Val	missense_variant	Exon 5 of 13	ENST00000298282.14	NP_001369252.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
PKNOX2	ENST00000298282.14	c.140C>T	p.Ala47Val	missense_variant	Exon 5 of 13	1	NM_001382323.2	ENSP00000298282.8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.068	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.011	T;T
Eigen	Benign	-0.17
Eigen_PC	Benign	-0.039
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.88	D;D
M_CAP	Benign	0.020	T
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PhyloP100		7.1
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.78	N;N
REVEL	Benign	0.075
Sift	Benign	0.15	T;T
Sift4G	Benign	0.34	T;T
Polyphen		0.19	B;.
Vest4		0.46
MutPred		0.13		Loss of glycosylation at P48 (P = 0.0936);Loss of glycosylation at P48 (P = 0.0936);
MVP		0.36
MPC		0.37
ClinPred		0.83	D
GERP RS		5.5
Varity_R		0.12
gMVP		0.33
Mutation Taster		=75/25	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: rs1295459678; hg19: chr11-125237794;