15-34152824-C-A

Position:

• chr15-34152824-C-A

Variant summary

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

The NM_024713.3(KATNBL1):​c.404G>T​(p.Ser135Ile) 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. 12/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: KATNBL1 NM_024713.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.84

Genes affected

KATNBL1 (HGNC:26199): (katanin regulatory subunit B1 like 1) Predicted to enable microtubule binding activity. Involved in positive regulation of cytoskeleton organization. Located in several cellular components, including cleavage furrow; mitotic spindle pole; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

KATNBL1 (HGNC:):

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=0.1605944).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNBL1	NM_024713.3	c.404G>T	p.Ser135Ile	missense_variant	4/10	ENST00000256544.8	NP_078989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KATNBL1	ENST00000256544.8	c.404G>T	p.Ser135Ile	missense_variant	4/10	1	NM_024713.3	ENSP00000256544.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 33

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

Oct 26, 2024

The c.404G>T (p.S135I) alteration is located in exon 4 (coding exon 3) of the KATNBL1 gene. This alteration results from a G to T substitution at nucleotide position 404, causing the serine (S) at amino acid position 135 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	0.11
BayesDel_addAF	Benign	-0.064	T
BayesDel_noAF	Benign	-0.33
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.024	T;.;T;.;T;T
Eigen	Benign	-0.16
Eigen_PC	Benign	-0.051
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.87	D;D;D;D;D;D
M_CAP	Benign	0.0066	T
MetaRNN	Benign	0.16	T;T;T;T;T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L;.;.;.;.;.
PrimateAI	Benign	0.39	T
PROVEAN	Benign	-1.3	N;D;D;D;D;D
REVEL	Benign	0.078
Sift	Uncertain	0.0060	D;D;D;D;D;D
Sift4G	Uncertain	0.047	D;T;.;.;.;D
Polyphen		0.38	B;.;.;.;.;.
Vest4		0.20
MutPred		0.25		Loss of phosphorylation at S135 (P = 0.0036);.;.;Loss of phosphorylation at S135 (P = 0.0036);.;Loss of phosphorylation at S135 (P = 0.0036);
MVP		0.27
MPC		0.31
ClinPred		0.87	D
GERP RS		2.2
Varity_R		0.23
gMVP		0.39

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-34445025;