KNCN p.Gly21Arg

Variant names:

• chr1-46551155-C-G
• NM_001322255.2:c.61G>C
• KNCN p.Gly21Arg

Your query was ambiguous. Multiple possible variants found:

• chr1-46551155-C-G
• chr1-46551155-C-T
• chr1-46551153-CCC-ACG
• chr1-46551153-CCC-GCG
• chr1-46551153-CCC-TCG
• chr1-46551153-CCC-TCT

Variant summary

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

The NM_001322255.2(KNCN):​c.61G>C​(p.Gly21Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: KNCN NM_001322255.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.714
• Publications: 0 publications found

Genes affected

KNCN (HGNC:26488): (kinocilin) Predicted to be located in apical part of cell; cytoplasm; and microtubule cytoskeleton. Predicted to be active in several cellular components, including apical plasma membrane; cytoskeleton; and kinocilium. [provided by Alliance of Genome Resources, Apr 2022]

MKNK1-AS1 (HGNC:44129): (MKNK1 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001322255.2. 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
	KNCN	NM_001322255.2	MANE Select	c.61G>C	p.Gly21Arg	missense	Exon 1 of 4	NP_001309184.1	A6PVL3-1
	KNCN	NM_001097611.1		c.61G>C	p.Gly21Arg	missense	Exon 1 of 3	NP_001091080.1	A6PVL3-2
	MKNK1-AS1	NR_038403.1		n.255-7070C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KNCN	ENST00000481882.7	TSL:5 MANE Select	c.61G>C	p.Gly21Arg	missense	Exon 1 of 4	ENSP00000419705.3	A6PVL3-1
	KNCN	ENST00000396314.3	TSL:4	c.61G>C	p.Gly21Arg	missense	Exon 1 of 3	ENSP00000379607.3	A6PVL3-2
	MKNK1-AS1	ENST00000602433.1	TSL:2	n.255-7070C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.92
BayesDel_addAF	Uncertain	0.055	T
BayesDel_noAF	Benign	-0.16
CADD	Benign	16
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.47
Eigen_PC	Benign	-0.59
FATHMM_MKL	Benign	0.054	N
LIST_S2	Benign	0.59	T
M_CAP	Uncertain	0.086	D
MetaRNN	Uncertain	0.59	D
MetaSVM	Benign	-0.64	T
PhyloP100		-0.71
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.4	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0080	D
Sift4G	Uncertain	0.011	D
PromoterAI		0.0038	Neutral
Varity_R		0.41
gMVP		0.59
Mutation Taster		=93/7	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

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

Other links and lift over

hg19: chr1-47016827;