rs34998154

Variant names:

• chr15-34145451-C-A
• rs34998154
• NM_024713.3:c.829G>T

Your query was ambiguous. Multiple possible variants found:

• chr15-34145451-C-A
• chr15-34145451-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_024713.3(KATNBL1):​c.829G>T​(p.Glu277*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000763 in 1,311,468 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Variant results in nonsense mediated mRNA decay.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.6e-7 (0 hom.)
• Consequence: KATNBL1 NM_024713.3 stop_gained
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KATNBL1	NM_024713.3	c.829G>T	p.Glu277*	stop_gained	Exon 9 of 10	ENST00000256544.8	NP_078989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KATNBL1	ENST00000256544.8	c.829G>T	p.Glu277*	stop_gained	Exon 9 of 10	1	NM_024713.3	ENSP00000256544.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.63e-7 AC: 1 AN: 1311468 Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0 AN XY: 647560

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26140

American (AMR) AF: 0.00 AC: 0 AN: 20988

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21326

East Asian (EAS) AF: 0.00 AC: 0 AN: 32624

South Asian (SAS) AF: 0.0000173 AC: 1 AN: 57942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48862

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4976

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1045184

Other (OTH) AF: 0.00 AC: 0 AN: 53426

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Pathogenic	0.56	D
BayesDel_noAF	Pathogenic	0.57
CADD	Pathogenic	37
DANN	Uncertain	1.0
Eigen	Pathogenic	0.81
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Uncertain	0.84	D
PhyloP100		1.5
Vest4		0.31
GERP RS		4.3

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

Other links and lift over

dbSNP: rs34998154; hg19: chr15-34437652;