13-30208638-C-T

Variant names:

• chr13-30208638-C-T
• NM_032116.5:c.1375G>A

Variant summary

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

The NM_032116.5(KATNAL1):​c.1375G>A​(p.Gly459Arg) 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: 33)
• Consequence: KATNAL1 NM_032116.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.99
• Publications: 0 publications found

Genes affected

KATNAL1 (HGNC:28361): (katanin catalytic subunit A1 like 1) Enables identical protein binding activity and microtubule-severing ATPase activity. Involved in microtubule severing. Located in cytoplasm; microtubule; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

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=0.10262972).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032116.5. 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
	KATNAL1	NM_032116.5	MANE Select	c.1375G>A	p.Gly459Arg	missense	Exon 11 of 11	NP_115492.1	Q9BW62
	KATNAL1	NM_001014380.3		c.1375G>A	p.Gly459Arg	missense	Exon 11 of 11	NP_001014402.1	Q9BW62

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KATNAL1	ENST00000380615.8	TSL:1 MANE Select	c.1375G>A	p.Gly459Arg	missense	Exon 11 of 11	ENSP00000369989.3	Q9BW62
	KATNAL1	ENST00000908524.1		c.1393G>A	p.Gly465Arg	missense	Exon 11 of 11	ENSP00000578583.1
	KATNAL1	ENST00000908525.1		c.1393G>A	p.Gly465Arg	missense	Exon 11 of 11	ENSP00000578584.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

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	0.14
BayesDel_addAF	Uncertain	0.11	D
BayesDel_noAF	Uncertain	-0.080
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.22	T
Eigen	Benign	-0.14
Eigen_PC	Benign	0.15
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.066	D
MetaRNN	Benign	0.10	T
MetaSVM	Uncertain	-0.17	T
MutationAssessor	Benign	-0.44	N
PhyloP100		5.0
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	1.4	N
REVEL	Uncertain	0.37
Sift	Benign	0.37	T
Sift4G	Benign	0.40	T
Polyphen		0.0020	B
Vest4		0.43
MutPred		0.25		Gain of MoRF binding (P = 0.0165)
MVP		0.27
MPC		0.36
ClinPred		0.67	D
GERP RS		6.2
Varity_R		0.30
gMVP		0.51
Mutation Taster		=31/69	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

hg19: chr13-30782775;