chr10-87862096-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -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. 15/20 in silico tools predict 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: 0.0045 ( 57 hom. )

Consequence

KLLN
NM_001126049.2 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.171

Publications

8 publications found

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 Gene-Disease associations (from GenCC):

Cowden disease
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Cowden syndrome 4
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

KLLN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 [Likely_benign]. Clinvar id is 1337856.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High AC in GnomAd4 at 765 Unknown,AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLLN	NM_001126049.2 link	c.392A>G	p.Asn131Ser	missense_variant	Exon 1 of 1	ENST00000445946.5	NP_001119521.1	B2CW77

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLLN	ENST00000445946.5 link	c.392A>G	p.Asn131Ser	missense_variant	Exon 1 of 1	6	NM_001126049.2	ENSP00000392204.2		B2CW77

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

GnomAD2 exomes

AF:

0.00693

AC:

976

AN:

140928

AF XY:

0.00783

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 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

African (AFR)

AF:

0.00602

AC:

187

AN:

31062

American (AMR)

AF:

0.00375

AC:

127

AN:

33822

Ashkenazi Jewish (ASJ)

AF:

0.0221

AC:

523

AN:

23672

East Asian (EAS)

AF:

0.00126

AC:

AN:

35632

South Asian (SAS)

AF:

0.0207

AC:

1593

AN:

77096

European-Finnish (FIN)

AF:

0.00149

AC:

AN:

48484

Middle Eastern (MID)

AF:

0.0211

AC:

118

AN:

5584

European-Non Finnish (NFE)

AF:

0.00295

AC:

3160

AN:

1070424

Other (OTH)

AF:

0.00704

AC:

403

AN:

57228

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

368

735

1103

1470

1838

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00503

AC:

765

AN:

152206

Hom.:

Cov.:

AF XY:

0.00497

AC XY:

370

AN XY:

74426

show subpopulations

African (AFR)

AF:

0.00549

AC:

228

AN:

41560

American (AMR)

AF:

0.00601

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0237

AC:

AN:

3466

East Asian (EAS)

AF:

0.00484

AC:

AN:

5164

South Asian (SAS)

AF:

0.0195

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00132

AC:

AN:

10598

Middle Eastern (MID)

AF:

0.00680

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00322

AC:

219

AN:

67992

Other (OTH)

AF:

0.00427

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

109

146

182

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00463

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/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Nov 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

KLLN: BP4, BS1, BS2 -

not specified

Benign:1

Aug 25, 2020

Genetic Services Laboratory, University of Chicago

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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

(source)

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

PhyloP100

0.17

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

Mutation Taster

=99/1

polymorphism

(source)

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

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chr10-87862096-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over