Variant 10-87862096-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001126049.2(KLLN):c.392A>G(p.Asn131Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00456 in 1,535,210 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0045 ( 57 hom. )

Consequence

KLLN
NM_001126049.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.171

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0028946996).

BP6

Variant 10-87862096-T-C is Benign according to our data. Variant chr10-87862096-T-C is described in ClinVar as [Benign]. Clinvar id is 1337856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr10-87862096-T-C is described in Lovd as [Likely_benign].

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00503 (765/152206) while in subpopulation SAS AF= 0.0195 (94/4820). AF 95% confidence interval is 0.0163. There are 6 homozygotes in gnomad4. There are 370 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd at 761 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLLN	NM_001126049.2 linkuse as main transcript	c.392A>G	p.Asn131Ser	missense_variant	1/1	ENST00000445946.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLLN	ENST00000445946.5 linkuse as main transcript	c.392A>G	p.Asn131Ser	missense_variant	1/1		NM_001126049.2	P1

Frequencies

GnomAD3 genomes

AF:

0.00500

AC:

761

AN:

152088

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00538

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00602

Gnomad ASJ

AF:

0.0237

Gnomad EAS

AF:

0.00483

Gnomad SAS

AF:

0.0197

Gnomad FIN

AF:

0.00132

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00322

Gnomad OTH

AF:

0.00432

GnomAD3 exomes

AF:

0.00693

AC:

976

AN:

140928

Hom.:

AF XY:

0.00783

AC XY:

583

AN XY:

74432

show subpopulations

Gnomad AFR exome

AF:

0.00566

Gnomad AMR exome

AF:

0.00366

Gnomad ASJ exome

AF:

0.0211

Gnomad EAS exome

AF:

0.00350

Gnomad SAS exome

AF:

0.0202

Gnomad FIN exome

AF:

0.00161

Gnomad NFE exome

AF:

0.00383

Gnomad OTH exome

AF:

0.00561

GnomAD4 exome

AF:

0.00450

AC:

6228

AN:

1383004

Hom.:

Cov.:

AF XY:

0.00493

AC XY:

3356

AN XY:

680808

show subpopulations

Gnomad4 AFR exome

AF:

0.00602

Gnomad4 AMR exome

AF:

0.00375

Gnomad4 ASJ exome

AF:

0.0221

Gnomad4 EAS exome

AF:

0.00126

Gnomad4 SAS exome

AF:

0.0207

Gnomad4 FIN exome

AF:

0.00149

Gnomad4 NFE exome

AF:

0.00295

Gnomad4 OTH exome

AF:

0.00704

GnomAD4 genome

AF:

0.00503

AC:

765

AN:

152206

Hom.:

Cov.:

AF XY:

0.00497

AC XY:

370

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.00549

Gnomad4 AMR

AF:

0.00601

Gnomad4 ASJ

AF:

0.0237

Gnomad4 EAS

AF:

0.00484

Gnomad4 SAS

AF:

0.0195

Gnomad4 FIN

AF:

0.00132

Gnomad4 NFE

AF:

0.00322

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00460

Hom.:

Bravo

AF:

0.00462

ESP6500AA

AF:

0.00506

AC:

ESP6500EA

AF:

0.00220

AC:

ExAC

AF:

0.0103

AC:

249

Asia WGS

AF:

0.0120

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Aug 25, 2020

- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2023

KLLN: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.030

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.56

Cadd

Benign

Dann

Benign

0.78

DEOGEN2

Benign

0.00093

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.0023

MetaRNN

Benign

0.0029

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

MutationTaster

Benign

1.0

PrimateAI

Benign

0.44

PROVEAN

Benign

2.7

REVEL

Benign

0.028

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.052

ClinPred

0.016

GERP RS

1.3

Varity_R

0.039

gMVP

0.0017

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