rs755558823

Variant names:

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

Your query was ambiguous. Multiple possible variants found:

• chr1-46551182-C-T
• chr1-46551182-C-A
• chr1-46551182-C-G

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>A​(p.Gly12Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000404 in 1,610,052 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: KNCN NM_001322255.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• 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=0.1634996).

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.34G>A	p.Gly12Ser	missense	Exon 1 of 4	NP_001309184.1	A6PVL3-1
	KNCN	NM_001097611.1		c.34G>A	p.Gly12Ser	missense	Exon 1 of 3	NP_001091080.1	A6PVL3-2
	MKNK1-AS1	NR_038403.1		n.255-7043C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KNCN	ENST00000481882.7	TSL:5 MANE Select	c.34G>A	p.Gly12Ser	missense	Exon 1 of 4	ENSP00000419705.3	A6PVL3-1
	KNCN	ENST00000396314.3	TSL:4	c.34G>A	p.Gly12Ser	missense	Exon 1 of 3	ENSP00000379607.3	A6PVL3-2
	MKNK1-AS1	ENST00000602433.1	TSL:2	n.255-7043C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152208 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000451 AC: 11 AN: 243944 AF XY: 0.0000226

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000904

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000405 AC: 59 AN: 1457844 Hom.: 0 Cov.: 31 AF XY: 0.0000331 AC XY: 24 AN XY: 725196

African (AFR) AF: 0.0000301 AC: 1 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: 0.0000584 AC: 5 AN: 85654

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53138

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

European-Non Finnish (NFE) AF: 0.0000459 AC: 51 AN: 1110332

Other (OTH) AF: 0.0000166 AC: 1 AN: 60236

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152208 Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1 AN XY: 74358

African (AFR) AF: 0.00 AC: 0 AN: 41452

American (AMR) AF: 0.0000654 AC: 1 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68038

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000712 Hom.: 0

Bravo AF: 0.0000491

ExAC AF: 0.0000496 AC: 6

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	0.10
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0065	T
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.29
FATHMM_MKL	Benign	0.54	D
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.16	T
MetaSVM	Benign	-0.91	T
PhyloP100		2.4
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	0.51	N
REVEL	Benign	0.14
Sift	Benign	0.23	T
Sift4G	Benign	0.062	T
Polyphen		0.0	B
Vest4		0.37
MutPred		0.21		Loss of catalytic residue at G12 (P = 0.0242)
MVP		0.18
MPC		0.089
ClinPred		0.10	T
GERP RS		5.4
PromoterAI		-0.028	Neutral
Varity_R		0.039
gMVP		0.31
Mutation Taster		=97/3	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;