6-149603289-C-A

Variant names:

• chr6-149603289-C-A
• rs1250564677
• NM_007044.4:c.708G>T

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_007044.4(KATNA1):​c.708G>T​(p.Lys236Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: -0.331
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3939296).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_007044.4. 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
	KATNA1	NM_007044.4	MANE Select	c.708G>T	p.Lys236Asn	missense	Exon 6 of 11	NP_008975.1	O75449-1
	KATNA1	NM_001204076.2		c.502-1537G>T		intron	N/A	NP_001191005.1	O75449-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNA1	ENST00000367411.7	TSL:2 MANE Select	c.708G>T	p.Lys236Asn	missense	Exon 6 of 11	ENSP00000356381.2	O75449-1
	KATNA1	ENST00000335647.9	TSL:1	c.708G>T	p.Lys236Asn	missense	Exon 5 of 10	ENSP00000335106.5	O75449-1
	KATNA1	ENST00000335643.12	TSL:1	c.502-1537G>T		intron	N/A	ENSP00000335180.8	O75449-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 24

GnomAD4 genome Cov.: 32

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	Pathogenic	0.86
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.20
Eigen_PC	Benign	-0.27
FATHMM_MKL	Benign	0.62	D
LIST_S2	Uncertain	0.97	D
M_CAP	Uncertain	0.14	D
MetaRNN	Benign	0.39	T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Uncertain	2.8	M
PhyloP100		-0.33
PrimateAI	Pathogenic	0.82	D
PROVEAN	Uncertain	-3.9	D
REVEL	Uncertain	0.45
Sift	Uncertain	0.0020	D
Sift4G	Uncertain	0.0060	D
Polyphen		0.86	P
Vest4		0.69
MutPred		0.47		Loss of methylation at K236 (P = 0.0011)
MVP		0.98
MPC		0.53
ClinPred		0.99	D
GERP RS		0.20
Varity_R		0.88
gMVP		0.92
Mutation Taster		=32/68	disease causing

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: rs1250564677; hg19: chr6-149924425;