NM_004571.5:c.93C>G

Variant names:

• chr21-43007532-C-G
• NM_004571.5:c.93C>G

Variant summary

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

The NM_004571.5(PKNOX1):​c.93C>G​(p.Asn31Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PKNOX1 NM_004571.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.844
• Publications: 0 publications found

Genes affected

PKNOX1 (HGNC:9022): (PBX/knotted 1 homeobox 1) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in angiogenesis and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within camera-type eye development; hemopoiesis; and positive regulation of transcription by RNA polymerase II. Predicted to be located in cytoplasm and nucleus. Predicted to be part of chromatin. [provided by Alliance of Genome Resources, Apr 2022]

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=0.09253198).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004571.5. 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
	PKNOX1	NM_004571.5	MANE Select	c.93C>G	p.Asn31Lys	missense	Exon 3 of 11	NP_004562.2
	PKNOX1	NM_001320694.2		c.93C>G	p.Asn31Lys	missense	Exon 3 of 11	NP_001307623.1
	PKNOX1	NM_001286258.2		c.-87C>G		5_prime_UTR	Exon 3 of 10	NP_001273187.1	E7EPN6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PKNOX1	ENST00000291547.10	TSL:1 MANE Select	c.93C>G	p.Asn31Lys	missense	Exon 3 of 11	ENSP00000291547.4	P55347-1
	PKNOX1	ENST00000911566.1		c.93C>G	p.Asn31Lys	missense	Exon 3 of 12	ENSP00000581625.1
	PKNOX1	ENST00000883907.1		c.93C>G	p.Asn31Lys	missense	Exon 3 of 12	ENSP00000553966.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.093
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	12
DANN	Benign	0.87
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.61
Eigen_PC	Benign	-0.53
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.44	T
M_CAP	Benign	0.0035	T
MetaRNN	Benign	0.093	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	-0.55	N
PhyloP100		0.84
PrimateAI	Benign	0.36	T
PROVEAN	Benign	-0.69	N
REVEL	Benign	0.018
Sift	Benign	0.63	T
Sift4G	Benign	0.86	T
Polyphen		0.042	B
Vest4		0.31
MutPred		0.27		Gain of methylation at N31 (P = 0.0022)
MVP		0.31
MPC		0.39
ClinPred		0.043	T
GERP RS		1.9
Varity_R		0.070
gMVP		0.079
Mutation Taster		=95/5	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

hg19: chr21-44427642;