6-149603342-T-G

Position:

• chr6-149603342-T-G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007044.4(KATNA1):​c.655A>C​(p.Lys219Gln) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 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: 6.17

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.42084473).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNA1	NM_007044.4	c.655A>C	p.Lys219Gln	missense_variant	6/11	ENST00000367411.7	NP_008975.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KATNA1	ENST00000367411.7	c.655A>C	p.Lys219Gln	missense_variant	6/11	2	NM_007044.4	ENSP00000356381	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 25

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

Jun 06, 2023

The c.655A>C (p.K219Q) alteration is located in exon 6 (coding exon 5) of the KATNA1 gene. This alteration results from a A to C substitution at nucleotide position 655, causing the lysine (K) at amino acid position 219 to be replaced by a glutamine (Q). 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	0.091
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Pathogenic	27
DANN	Uncertain	0.99
DEOGEN2	Benign	0.070	T;T;T
Eigen	Uncertain	0.42
Eigen_PC	Uncertain	0.51
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.95	.;D;D
M_CAP	Uncertain	0.12	D
MetaRNN	Benign	0.42	T;T;T
MetaSVM	Uncertain	0.50	D
MutationAssessor	Uncertain	2.2	M;M;.
MutationTaster	Benign	1.0	D;D;D
PrimateAI	Uncertain	0.78	T
PROVEAN	Benign	-1.8	N;N;N
REVEL	Uncertain	0.53
Sift	Uncertain	0.010	D;D;D
Sift4G	Benign	0.27	T;T;.
Polyphen		0.97	D;D;.
Vest4		0.45
MutPred		0.33		Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);Loss of helix (P = 0.0558);
MVP		0.98
MPC		0.69
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.62
gMVP		0.86

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: chr6-149924478;