15-34152986-T-C

Position:

• chr15-34152986-T-C

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_024713.3(KATNBL1):​c.242A>G​(p.Asn81Ser) 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. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: KATNBL1 NM_024713.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.962

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04562241).
• BP6: Variant 15-34152986-T-C is Benign according to our data. Variant chr15-34152986-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 2239174.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KATNBL1	NM_024713.3	c.242A>G	p.Asn81Ser	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.242A>G	p.Asn81Ser	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: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 21, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.30	T
BayesDel_noAF	Benign	-0.67
CADD	Benign	8.3
DANN	Benign	0.72
DEOGEN2	Benign	0.0023	T;.;.;T
Eigen	Benign	-0.96
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.53	D
LIST_S2	Benign	0.74	T;T;T;T
M_CAP	Benign	0.00096	T
MetaRNN	Benign	0.046	T;T;T;T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.0	L;.;.;.
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.62	N;N;N;N
REVEL	Benign	0.095
Sift	Benign	0.39	T;T;T;T
Sift4G	Benign	0.68	T;T;.;T
Polyphen		0.0010	B;.;.;.
Vest4		0.10
MutPred		0.21		Gain of glycosylation at N81 (P = 0.0258);.;Gain of glycosylation at N81 (P = 0.0258);Gain of glycosylation at N81 (P = 0.0258);
MVP		0.12
MPC		0.087
ClinPred		0.089	T
GERP RS		2.1
Varity_R		0.018
gMVP		0.10

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: chr15-34445187;