chr6-149623146-C-T

Variant names:

• chr6-149623146-C-T
• rs369384760
• NM_007044.4:c.458G>A

Variant summary

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

The NM_007044.4(KATNA1):​c.458G>A​(p.Arg153His) variant causes a missense change. The variant allele was found at a frequency of 0.0000827 in 1,608,878 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R153C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000081 (1 hom.)
• Consequence: KATNA1 NM_007044.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.03
• 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24706194).

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.458G>A	p.Arg153His	missense	Exon 4 of 11	NP_008975.1	O75449-1
	KATNA1	NM_001204076.2		c.458G>A	p.Arg153His	missense	Exon 4 of 8	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.458G>A	p.Arg153His	missense	Exon 4 of 11	ENSP00000356381.2	O75449-1
	KATNA1	ENST00000335647.9	TSL:1	c.458G>A	p.Arg153His	missense	Exon 3 of 10	ENSP00000335106.5	O75449-1
	KATNA1	ENST00000335643.12	TSL:1	c.458G>A	p.Arg153His	missense	Exon 4 of 8	ENSP00000335180.8	O75449-2

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152132 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000852 AC: 21 AN: 246432 AF XY: 0.0000902

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000549

Gnomad FIN exome AF: 0.000371

Gnomad NFE exome AF: 0.0000800

Gnomad OTH exome AF: 0.000332

GnomAD4 exome AF: 0.0000810 AC: 118 AN: 1456628 Hom.: 1 Cov.: 30 AF XY: 0.0000718 AC XY: 52 AN XY: 724426

African (AFR) AF: 0.00 AC: 0 AN: 33228

American (AMR) AF: 0.00 AC: 0 AN: 43200

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25954

East Asian (EAS) AF: 0.00 AC: 0 AN: 39660

South Asian (SAS) AF: 0.0000236 AC: 2 AN: 84584

European-Finnish (FIN) AF: 0.000412 AC: 22 AN: 53380

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5744

European-Non Finnish (NFE) AF: 0.0000765 AC: 85 AN: 1110634

Other (OTH) AF: 0.000149 AC: 9 AN: 60244

GnomAD4 genome AF: 0.0000985 AC: 15 AN: 152250 Hom.: 0 Cov.: 32 AF XY: 0.000121 AC XY: 9 AN XY: 74450

African (AFR) AF: 0.00 AC: 0 AN: 41542

American (AMR) AF: 0.00 AC: 0 AN: 15280

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

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.000283 AC: 3 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000162 AC: 11 AN: 68028

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.000160 Hom.: 0

Bravo AF: 0.0000869

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000741 AC: 9

EpiCase AF: 0.0000546

EpiControl AF: 0.00

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	0.12
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Pathogenic	0.21
CADD	Uncertain	25
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.20
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.19	D
MetaRNN	Benign	0.25	T
MetaSVM	Uncertain	0.43	D
MutationAssessor	Uncertain	2.1	M
PhyloP100		5.0
PrimateAI	Uncertain	0.62	T
PROVEAN	Benign	-1.6	N
REVEL	Uncertain	0.61
Sift	Benign	0.10	T
Sift4G	Benign	0.12	T
Polyphen		0.83	P
Vest4		0.56
MVP		0.96
MPC		1.1
ClinPred		0.17	T
GERP RS		5.0
Varity_R		0.16
gMVP		0.33
Mutation Taster		=54/46	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: rs369384760; hg19: chr6-149944282;