Variant 15-40389569-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The ENST00000249776.13(KNSTRN):c.549A>G(p.Glu183Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000178 in 1,614,172 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 Likely benign (★).

Frequency

Genomes: 𝑓 0.00098 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000095 ( 0 hom. )

Consequence

KNSTRN
ENST00000249776.13 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.43

Variant links:

Genes affected

KNSTRN (HGNC:30767): (kinetochore localized astrin (SPAG5) binding protein) Enables microtubule plus-end binding activity and protein homodimerization activity. Involved in several processes, including cellular response to epidermal growth factor stimulus; mitotic sister chromatid segregation; and regulation of attachment of spindle microtubules to kinetochore. Located in several cellular components, including kinetochore; microtubule cytoskeleton; and ruffle. Implicated in actinic keratosis and skin squamous cell carcinoma. [provided by Alliance of Genome Resources, Apr 2022]

KNSTRN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.66).

BP6

Variant 15-40389569-A-G is Benign according to our data. Variant chr15-40389569-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 2645171.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=1.43 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KNSTRN	NM_033286.4 linkuse as main transcript	c.549A>G	p.Glu183Glu	synonymous_variant	5/9	ENST00000249776.13	NP_150628.3	Q9Y448-1
KNSTRN	NM_001142761.1 linkuse as main transcript	c.549A>G	p.Glu183Glu	synonymous_variant	5/9		NP_001136233.1	Q9Y448-2
KNSTRN	NM_001142762.1 linkuse as main transcript	c.549A>G	p.Glu183Glu	synonymous_variant	5/8		NP_001136234.1	Q9Y448-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KNSTRN	ENST00000249776.13 linkuse as main transcript	c.549A>G	p.Glu183Glu	synonymous_variant	5/9	1	NM_033286.4	ENSP00000249776.8		Q9Y448-1

Frequencies

GnomAD3 genomes

AF:

0.000985

AC:

150

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00355

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000221

AC:

AN:

249340

Hom.:

AF XY:

0.000177

AC XY:

AN XY:

135334

show subpopulations

Gnomad AFR exome

AF:

0.00324

Gnomad AMR exome

AF:

0.000145

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000951

AC:

139

AN:

1461814

Hom.:

Cov.:

AF XY:

0.0000756

AC XY:

AN XY:

727208

show subpopulations

Gnomad4 AFR exome

AF:

0.00346

Gnomad4 AMR exome

AF:

0.000201

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:

0.000215

GnomAD4 genome

AF:

0.000978

AC:

149

AN:

152358

Hom.:

Cov.:

AF XY:

0.000899

AC XY:

AN XY:

74502

show subpopulations

Gnomad4 AFR

AF:

0.00351

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000749

Hom.:

Bravo

AF:

0.00126

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Sep 01, 2023

KNSTRN: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.66

CADD

Benign

7.0

DANN

Benign

0.51

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over