rs1873372454

Variant names:

• chr13-30208640-T-A
• rs1873372454
• NM_032116.5:c.1373A>T

Your query was ambiguous. Multiple possible variants found:

• chr13-30208640-T-A
• chr13-30208640-T-C
• chr13-30208640-T-G

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.1373A>T​(p.Lys458Ile) 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. 13/22 in silico tools predict 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: 0.128
• 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=0.112888396).

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.1373A>T	p.Lys458Ile	missense	Exon 11 of 11	NP_115492.1	Q9BW62
	KATNAL1	NM_001014380.3		c.1373A>T	p.Lys458Ile	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.1373A>T	p.Lys458Ile	missense	Exon 11 of 11	ENSP00000369989.3	Q9BW62
	KATNAL1	ENST00000908524.1		c.1391A>T	p.Lys464Ile	missense	Exon 11 of 11	ENSP00000578583.1
	KATNAL1	ENST00000908525.1		c.1391A>T	p.Lys464Ile	missense	Exon 11 of 11	ENSP00000578584.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

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	0.19
BayesDel_addAF	Uncertain	0.082	D
BayesDel_noAF	Benign	-0.12
CADD	Benign	17
DANN	Uncertain	0.98
DEOGEN2	Benign	0.24	T
Eigen	Benign	-0.75
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.049	D
MetaRNN	Benign	0.11	T
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Benign	-0.49	N
PhyloP100		0.13
PrimateAI	Benign	0.30	T
PROVEAN	Benign	-0.11	N
REVEL	Uncertain	0.37
Sift	Benign	0.094	T
Sift4G	Benign	0.29	T
Polyphen		0.0	B
Vest4		0.36
MutPred		0.50		Loss of disorder (P = 0.0096)
MVP		0.47
MPC		0.57
ClinPred		0.65	D
GERP RS		-4.3
Varity_R		0.091
gMVP		0.46
Mutation Taster		=78/22	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: rs1873372454; hg19: chr13-30782777;