NM_007044.4:c.404G>C

Variant names:

• chr6-149623200-C-G
• rs141453341
• NM_007044.4:c.404G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS2

The NM_007044.4(KATNA1):​c.404G>C​(p.Arg135Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,613,748 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00096 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (2 hom.)
• Consequence: KATNA1 NM_007044.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.17
• Publications: 6 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.026744872).
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

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.404G>C	p.Arg135Thr	missense	Exon 4 of 11	NP_008975.1	O75449-1
	KATNA1	NM_001204076.2		c.404G>C	p.Arg135Thr	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.404G>C	p.Arg135Thr	missense	Exon 4 of 11	ENSP00000356381.2	O75449-1
	KATNA1	ENST00000335647.9	TSL:1	c.404G>C	p.Arg135Thr	missense	Exon 3 of 10	ENSP00000335106.5	O75449-1
	KATNA1	ENST00000335643.12	TSL:1	c.404G>C	p.Arg135Thr	missense	Exon 4 of 8	ENSP00000335180.8	O75449-2

Frequencies

GnomAD3 genomes AF: 0.000960 AC: 146 AN: 152126 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000197

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000754

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00171

Gnomad OTH AF: 0.000957

GnomAD2 exomes AF: 0.000991 AC: 249 AN: 251218 AF XY: 0.00100

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.0000870

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000647

Gnomad NFE exome AF: 0.00196

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.00154 AC: 2251 AN: 1461504 Hom.: 2 Cov.: 30 AF XY: 0.00148 AC XY: 1079 AN XY: 727074

African (AFR) AF: 0.0000299 AC: 1 AN: 33466

American (AMR) AF: 0.000112 AC: 5 AN: 44664

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39690

South Asian (SAS) AF: 0.00 AC: 0 AN: 86196

European-Finnish (FIN) AF: 0.00109 AC: 58 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00191 AC: 2124 AN: 1111786

Other (OTH) AF: 0.00104 AC: 63 AN: 60388

GnomAD4 genome AF: 0.000959 AC: 146 AN: 152244 Hom.: 0 Cov.: 32 AF XY: 0.000954 AC XY: 71 AN XY: 74448

African (AFR) AF: 0.000409 AC: 17 AN: 41554

American (AMR) AF: 0.000196 AC: 3 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.000754 AC: 8 AN: 10606

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

European-Non Finnish (NFE) AF: 0.00171 AC: 116 AN: 68018

Other (OTH) AF: 0.000947 AC: 2 AN: 2112

Alfa AF: 0.00146 Hom.: 0

Bravo AF: 0.000763

TwinsUK AF: 0.00135 AC: 5

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.000908 AC: 4

ESP6500EA AF: 0.00163 AC: 14

ExAC AF: 0.00127 AC: 154

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00169

EpiControl AF: 0.00142

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	0.23
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Uncertain	0.030
CADD	Benign	22
DANN	Benign	0.97
DEOGEN2	Benign	0.022	T
Eigen	Benign	-0.032
Eigen_PC	Benign	0.16
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Benign	0.83	T
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.027	T
MetaSVM	Uncertain	-0.044	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		2.2
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-0.12	N
REVEL	Uncertain	0.40
Sift	Benign	0.20	T
Sift4G	Benign	0.13	T
Polyphen		0.0010	B
Vest4		0.53
MVP		0.97
MPC		0.70
ClinPred		0.015	T
GERP RS		4.9
Varity_R		0.12
gMVP		0.38
Mutation Taster		=77/23	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs141453341; hg19: chr6-149944336;