1-46551182-C-G

Variant names:

• chr1-46551182-C-G
• rs755558823
• NM_001322255.2:c.34G>C

Variant summary

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

The NM_001322255.2(KNCN):​c.34G>C​(p.Gly12Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000165 in 1,457,844 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. G12S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: KNCN NM_001322255.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.35
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2504514).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KNCN	NM_001322255.2	c.34G>C	p.Gly12Arg	missense_variant	Exon 1 of 4	ENST00000481882.7	NP_001309184.1
KNCN	NM_001097611.1	c.34G>C	p.Gly12Arg	missense_variant	Exon 1 of 3		NP_001091080.1
MKNK1-AS1	NR_038403.1	n.255-7043C>G		intron_variant	Intron 3 of 7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KNCN	ENST00000481882.7	c.34G>C	p.Gly12Arg	missense_variant	Exon 1 of 4	5	NM_001322255.2	ENSP00000419705.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.0000165 AC: 24 AN: 1457844 Hom.: 0 Cov.: 31 AF XY: 0.0000179 AC XY: 13 AN XY: 725196

African (AFR) AF: 0.00 AC: 0 AN: 33246

American (AMR) AF: 0.00 AC: 0 AN: 44200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26028

East Asian (EAS) AF: 0.00 AC: 0 AN: 39258

South Asian (SAS) AF: 0.00 AC: 0 AN: 85654

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53138

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000216 AC: 24 AN: 1110332

Other (OTH) AF: 0.00 AC: 0 AN: 60236

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.044	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	21
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0073	T;.
Eigen	Benign	-0.39
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.45	T;T
M_CAP	Benign	0.076	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.85	T
PhyloP100		2.4
PrimateAI	Uncertain	0.65	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.16
Sift	Benign	0.046	D;D
Sift4G	Uncertain	0.012	D;D
Polyphen		0.0020	.;B
Vest4		0.46
MutPred		0.27		Gain of helix (P = 0.0496);Gain of helix (P = 0.0496);
MVP		0.34
MPC		0.11
ClinPred		0.74	D
GERP RS		5.4
PromoterAI		-0.0040	Neutral
Varity_R		0.076
gMVP		0.36
Mutation Taster		=98/2	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: rs755558823; hg19: chr1-47016854;