13-30283646-T-A

Variant names:

• chr13-30283646-T-A
• NM_032116.5:c.132A>T

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.132A>T​(p.Arg44Ser) 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. 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: 0.489

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]

ENSG00000309792 (HGNC:):

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=0.19215506).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KATNAL1	NM_032116.5	c.132A>T	p.Arg44Ser	missense_variant	Exon 2 of 11	ENST00000380615.8	NP_115492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KATNAL1	ENST00000380615.8	c.132A>T	p.Arg44Ser	missense_variant	Exon 2 of 11	1	NM_032116.5	ENSP00000369989.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 28, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.132A>T (p.R44S) alteration is located in exon 2 (coding exon 1) of the KATNAL1 gene. This alteration results from a A to T substitution at nucleotide position 132, causing the arginine (R) at amino acid position 44 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.43
BayesDel_addAF	Uncertain	0.15	D
BayesDel_noAF	Uncertain	-0.030
CADD	Benign	17
DANN	Benign	0.97
DEOGEN2	Benign	0.021	T;T;.;.
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.59
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	.;D;D;D
M_CAP	Benign	0.021	T
MetaRNN	Benign	0.19	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.8	L;L;.;.
PhyloP100		0.49
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.39	N;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.72	T;T;T;T
Sift4G	Benign	0.75	T;T;T;.
Polyphen		0.049	B;B;.;.
Vest4		0.73
MutPred		0.47		Loss of MoRF binding (P = 0.0285);Loss of MoRF binding (P = 0.0285);Loss of MoRF binding (P = 0.0285);Loss of MoRF binding (P = 0.0285);
MVP		0.85
MPC		0.35
ClinPred		0.21	T
GERP RS		0.36
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.18
gMVP		0.56
Mutation Taster		=36/64	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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Other links and lift over

hg19: chr13-30857783;