13-30210370-T-A

Position:

• chr13-30210370-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_032116.5(KATNAL1):​c.1220A>T​(p.Asp407Val) 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. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: KATNAL1 NM_032116.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.16

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

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.17392042).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNAL1	NM_032116.5	c.1220A>T	p.Asp407Val	missense_variant	10/11	ENST00000380615.8	NP_115492.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KATNAL1	ENST00000380615.8	c.1220A>T	p.Asp407Val	missense_variant	10/11	1	NM_032116.5	ENSP00000369989	P1
KATNAL1	ENST00000380617.7	c.1220A>T	p.Asp407Val	missense_variant	10/11	2		ENSP00000369991	P1
KATNAL1	ENST00000480854.1	n.295A>T		non_coding_transcript_exon_variant	1/2	3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000756

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Sep 25, 2023

The c.1220A>T (p.D407V) alteration is located in exon 10 (coding exon 9) of the KATNAL1 gene. This alteration results from a A to T substitution at nucleotide position 1220, causing the aspartic acid (D) at amino acid position 407 to be replaced by a valine (V). 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	Benign	0.068
BayesDel_addAF	Uncertain	0.016	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Benign	0.095	T;T
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.023
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.88	.;D
M_CAP	Benign	0.059	D
MetaRNN	Benign	0.17	T;T
MetaSVM	Uncertain	-0.0031	T
MutationAssessor	Benign	0.47	N;N
MutationTaster	Benign	1.0	D;D
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.7	N;N
REVEL	Benign	0.28
Sift	Benign	0.28	T;T
Sift4G	Benign	0.33	T;T
Polyphen		0.0	B;B
Vest4		0.22
MutPred		0.54		Gain of helix (P = 0.0425);Gain of helix (P = 0.0425);
MVP		0.39
MPC		0.43
ClinPred		0.43	T
GERP RS		5.8
Varity_R		0.32
gMVP		0.83

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

LitVar

Other links and lift over

dbSNP: rs1285805031; hg19: chr13-30784507;