Variant 10-87862043-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_001126049.2(KLLN):c.445T>A(p.Trp149Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00446 in 1,490,586 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0044 ( 57 hom. )

Consequence

KLLN
NM_001126049.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.290

Variant links:

Genes affected

KLLN (HGNC:37212): (killin, p53 regulated DNA replication inhibitor) The protein encoded by this intronless gene is found in the nucleus, where it can inhibit DNA synthesis and promote S phase arrest coupled to apoptosis. The expression of this DNA binding protein is upregulated by transcription factor p53. [provided by RefSeq, Dec 2012]

KLLN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 10-87862043-A-T is Benign according to our data. Variant chr10-87862043-A-T is described in ClinVar as [Likely_benign]. Clinvar id is 1337818.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-87862043-A-T is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00504 (767/152320) while in subpopulation SAS AF= 0.0197 (95/4832). AF 95% confidence interval is 0.0165. There are 6 homozygotes in gnomad4. There are 372 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 767 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLLN	NM_001126049.2 linkuse as main transcript	c.445T>A	p.Trp149Arg	missense_variant	1/1	ENST00000445946.5	NP_001119521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLLN	ENST00000445946.5 linkuse as main transcript	c.445T>A	p.Trp149Arg	missense_variant	1/1		NM_001126049.2	ENSP00000392204	P1

Frequencies

GnomAD3 genomes

AF:

0.00501

AC:

763

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00538

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.0236

Gnomad EAS

AF:

0.00483

Gnomad SAS

AF:

0.0199

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00323

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00654

AC:

675

AN:

103242

Hom.:

AF XY:

0.00719

AC XY:

380

AN XY:

52868

show subpopulations

Gnomad AFR exome

AF:

0.00537

Gnomad AMR exome

AF:

0.00444

Gnomad ASJ exome

AF:

0.0215

Gnomad EAS exome

AF:

0.00351

Gnomad SAS exome

AF:

0.0210

Gnomad FIN exome

AF:

0.00169

Gnomad NFE exome

AF:

0.00376

Gnomad OTH exome

AF:

0.00640

GnomAD4 exome

AF:

0.00440

AC:

5887

AN:

1338266

Hom.:

Cov.:

AF XY:

0.00478

AC XY:

3128

AN XY:

654270

show subpopulations

Gnomad4 AFR exome

AF:

0.00594

Gnomad4 AMR exome

AF:

0.00418

Gnomad4 ASJ exome

AF:

0.0224

Gnomad4 EAS exome

AF:

0.00128

Gnomad4 SAS exome

AF:

0.0209

Gnomad4 FIN exome

AF:

0.00150

Gnomad4 NFE exome

AF:

0.00293

Gnomad4 OTH exome

AF:

0.00688

GnomAD4 genome

AF:

0.00504

AC:

767

AN:

152320

Hom.:

Cov.:

AF XY:

0.00499

AC XY:

372

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.00548

Gnomad4 AMR

AF:

0.00601

Gnomad4 ASJ

AF:

0.0236

Gnomad4 EAS

AF:

0.00484

Gnomad4 SAS

AF:

0.0197

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00323

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.00460

Hom.:

Bravo

AF:

0.00461

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00285

AC:

ESP6500AA

AF:

0.00578

AC:

ESP6500EA

AF:

0.00220

AC:

ExAC

AF:

0.00617

AC:

164

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Nov 01, 2023	KLLN: BS1, BS2 -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 25, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.62

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.073

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.079

MetaRNN

Benign

0.0049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.52

PROVEAN

Pathogenic

-13

REVEL

Benign

0.081

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.053

Vest4

0.52

MutPred

0.27

Gain of disorder (P = 0.0032);

MVP

0.19

ClinPred

0.065

GERP RS

0.22

Varity_R

0.45

gMVP

0.020

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.32

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.32

Position offset: -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