rs1392966855

Variant names:

• chr1-46547744-C-G
• NM_001322255.2:c.361G>C

Your query was ambiguous. Multiple possible variants found:

• chr1-46547744-C-G
• chr1-46547744-C-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001322255.2(KNCN):​c.361G>C​(p.Ala121Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000751 in 1,331,658 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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. A121D) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: KNCN NM_001322255.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.83

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04571727).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KNCN	NM_001322255.2	c.361G>C	p.Ala121Pro	missense_variant	Exon 4 of 4	ENST00000481882.7	NP_001309184.1
KNCN	NM_001097611.1	c.292G>C	p.Ala98Pro	missense_variant	Exon 3 of 3		NP_001091080.1
MKNK1-AS1	NR_038403.1	n.254+3976C>G		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KNCN	ENST00000481882.7	c.361G>C	p.Ala121Pro	missense_variant	Exon 4 of 4	5	NM_001322255.2	ENSP00000419705.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.51e-7 AC: 1 AN: 1331658 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 650418

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.53e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.077
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.64
CADD	Benign	1.2
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0058	T;.
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.037	N
LIST_S2	Benign	0.47	T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.046	T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.25	T
PROVEAN	Benign	-1.1	N;N
REVEL	Benign	0.025
Sift	Benign	0.20	T;T
Sift4G	Benign	0.27	T;T
Polyphen		0.0	.;B
Vest4		0.066
MutPred		0.076		.;Loss of MoRF binding (P = 0.0466);
MVP		0.014
MPC		0.13
ClinPred		0.090	T
GERP RS		-7.5
Varity_R		0.14
gMVP		0.035

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-47013416;