15-34152845-G-A

Position:

• chr15-34152845-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_024713.3(KATNBL1):​c.383C>T​(p.Ser128Phe) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: KATNBL1 NM_024713.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 8.39

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.2953087).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNBL1	NM_024713.3	c.383C>T	p.Ser128Phe	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.383C>T	p.Ser128Phe	missense_variant	4/10	1	NM_024713.3	ENSP00000256544.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461434 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727032

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: 0.00

Gnomad4 OTH exome AF: 0.00

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

Sep 08, 2024

The c.383C>T (p.S128F) alteration is located in exon 4 (coding exon 3) of the KATNBL1 gene. This alteration results from a C to T substitution at nucleotide position 383, causing the serine (S) at amino acid position 128 to be replaced by a phenylalanine (F). 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	0.12
BayesDel_addAF	Benign	0.011	T
BayesDel_noAF	Benign	-0.22
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.037	T;.;T;.;T;T
Eigen	Uncertain	0.29
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.90	D;D;D;D;D;D
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.30	T;T;T;T;T;T
MetaSVM	Benign	-0.71	T
MutationAssessor	Uncertain	2.1	M;.;.;.;.;.
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-0.81	N;D;D;D;D;D
REVEL	Benign	0.27
Sift	Uncertain	0.0040	D;D;D;D;D;D
Sift4G	Uncertain	0.021	D;D;.;.;.;D
Polyphen		0.27	B;.;.;.;.;.
Vest4		0.41
MutPred		0.29		Loss of sheet (P = 0.0025);.;.;Loss of sheet (P = 0.0025);.;Loss of sheet (P = 0.0025);
MVP		0.28
MPC		0.30
ClinPred		0.95	D
GERP RS		5.5
Varity_R		0.19
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: chr15-34445046;