chr13-30280183-C-A

Position:

• chr13-30280183-C-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.203G>T​(p.Ser68Ile) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,954 control chromosomes in the GnomAD database, with no homozygous occurrence. 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)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: KATNAL1 NM_032116.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.78

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=0.1696226).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KATNAL1	NM_032116.5	c.203G>T	p.Ser68Ile	missense_variant	3/11	ENST00000380615.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KATNAL1	ENST00000380615.8	c.203G>T	p.Ser68Ile	missense_variant	3/11	1	NM_032116.5	P1
KATNAL1	ENST00000380617.7	c.203G>T	p.Ser68Ile	missense_variant	3/11	2		P1
KATNAL1	ENST00000414289.5	c.203G>T	p.Ser68Ile	missense_variant	3/4	4
KATNAL1	ENST00000441394.1	c.203G>T	p.Ser68Ile	missense_variant	3/4	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457954 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 725334

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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

Jan 31, 2023

The c.203G>T (p.S68I) alteration is located in exon 3 (coding exon 2) of the KATNAL1 gene. This alteration results from a G to T substitution at nucleotide position 203, causing the serine (S) at amino acid position 68 to be replaced by an isoleucine (I). 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	0.16
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.088	T;T;.;.
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.94	.;D;D;D
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.17	T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.4	M;M;.;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Uncertain	0.63	T
PROVEAN	Benign	-2.1	N;N;D;D
REVEL	Benign	0.10
Sift	Benign	0.062	T;T;T;T
Sift4G	Benign	0.17	T;T;D;.
Polyphen		0.044	B;B;.;.
Vest4		0.59
MutPred		0.33		Loss of disorder (P = 0.0084);Loss of disorder (P = 0.0084);Loss of disorder (P = 0.0084);Loss of disorder (P = 0.0084);
MVP		0.37
MPC		0.37
ClinPred		0.76	D
GERP RS		3.6
Varity_R		0.11
gMVP		0.44

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-30854320;