6-149595064-T-C

Position:

• chr6-149595064-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_007044.4(KATNA1):​c.1448A>G​(p.Lys483Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KATNA1 NM_007044.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.26

Genes affected

KATNA1 (HGNC:6216): (katanin catalytic subunit A1) Microtubules, polymers of alpha and beta tubulin subunits, form the mitotic spindle of a dividing cell and help to organize membranous organelles during interphase. Katanin is a heterodimer that consists of a 60 kDa ATPase (p60 subunit A 1) and an 80 kDa accessory protein (p80 subunit B 1). The p60 subunit acts to sever and disassemble microtubules, while the p80 subunit targets the enzyme to the centrosome. This gene encodes the p80 subunit. This protein is a member of the AAA family of ATPases. Multiple alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Feb 2011]

RPS18P9 (HGNC:36483): (ribosomal protein S18 pseudogene 9)

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNA1	NM_007044.4	c.1448A>G	p.Lys483Arg	missense_variant	11/11	ENST00000367411.7	NP_008975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KATNA1	ENST00000367411.7	c.1448A>G	p.Lys483Arg	missense_variant	11/11	2	NM_007044.4	ENSP00000356381.2
KATNA1	ENST00000335647.9	c.1448A>G	p.Lys483Arg	missense_variant	10/10	1		ENSP00000335106.5
KATNA1	ENST00000335643	c.*157A>G		3_prime_UTR_variant	8/8	1		ENSP00000335180.8
RPS18P9	ENST00000648980.1	n.1398+525T>C		intron_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 03, 2024

The c.1448A>G (p.K483R) alteration is located in exon 11 (coding exon 10) of the KATNA1 gene. This alteration results from a A to G substitution at nucleotide position 1448, causing the lysine (K) at amino acid position 483 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.080
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.12
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.46	T;T
Eigen	Pathogenic	0.72
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.94	.;D
M_CAP	Uncertain	0.19	D
MetaRNN	Uncertain	0.55	D;D
MetaSVM	Pathogenic	1.1	D
MutationAssessor	Benign	1.7	L;L
PrimateAI	Uncertain	0.61	T
PROVEAN	Benign	-2.0	N;N
REVEL	Pathogenic	0.66
Sift	Uncertain	0.011	D;D
Sift4G	Uncertain	0.035	D;D
Polyphen		1.0	D;D
Vest4		0.46
MutPred		0.36		Loss of methylation at K483 (P = 0.0261);Loss of methylation at K483 (P = 0.0261);
MVP		0.97
MPC		1.0
ClinPred		0.92	D
GERP RS		5.9
Varity_R		0.49
gMVP		0.82

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: chr6-149916200;