13-30230503-C-A

Variant names:

• chr13-30230503-C-A
• rs1875990994
• NM_032116.5:c.977G>T

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_032116.5(KATNAL1):​c.977G>T​(p.Arg326Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: KATNAL1 NM_032116.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.91
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.942

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.977G>T	p.Arg326Leu	missense	Exon 8 of 11	NP_115492.1	Q9BW62
	KATNAL1	NM_001014380.3		c.977G>T	p.Arg326Leu	missense	Exon 8 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.977G>T	p.Arg326Leu	missense	Exon 8 of 11	ENSP00000369989.3	Q9BW62
	KATNAL1	ENST00000908524.1		c.995G>T	p.Arg332Leu	missense	Exon 8 of 11	ENSP00000578583.1
	KATNAL1	ENST00000908525.1		c.995G>T	p.Arg332Leu	missense	Exon 8 of 11	ENSP00000578584.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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	0.98
BayesDel_addAF	Pathogenic	0.47	D
BayesDel_noAF	Pathogenic	0.44
CADD	Pathogenic	34
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.72	D
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.86
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Benign	0.78	T
M_CAP	Pathogenic	0.47	D
MetaRNN	Pathogenic	0.94	D
MetaSVM	Pathogenic	1.0	D
MutationAssessor	Benign	1.9	L
PhyloP100		7.9
PrimateAI	Pathogenic	0.90	D
PROVEAN	Pathogenic	-6.8	D
REVEL	Pathogenic	0.94
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.018	D
Polyphen		1.0	D
Vest4		0.87
MutPred		0.72		Loss of disorder (P = 0.0444)
MVP		0.94
MPC		1.2
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.91
gMVP		0.91
Mutation Taster		=2/98	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs1875990994; hg19: chr13-30804640;