dbSNP rs1478683393: KLLN:p.Cys148Gly (chr10-87862046-A-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001126049.2(KLLN):c.442T>G(p.Cys148Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000747 in 1,338,130 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. C148R) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.5e-7 ( 0 hom. )

Consequence

KLLN
NM_001126049.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.600

Publications

2 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.049706668).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLLN	NM_001126049.2 link	c.442T>G	p.Cys148Gly	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.442T>G	p.Cys148Gly	missense_variant	Exon 1 of 1	6	NM_001126049.2	ENSP00000392204.2		B2CW77

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000971

AC:

AN:

102976

AF XY:

0.0000190

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000110

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

7.47e-7

AC:

AN:

1338130

Hom.:

Cov.:

AF XY:

0.00000153

AC XY:

AN XY:

654192

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29428

American (AMR)

AF:

0.00

AC:

AN:

25954

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20584

East Asian (EAS)

AF:

0.0000283

AC:

AN:

35276

South Asian (SAS)

AF:

0.00

AC:

AN:

69864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

46666

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5362

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1049858

Other (OTH)

AF:

0.00

AC:

AN:

55138

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.36

CADD

Benign

8.9

(source)

DANN

Benign

0.64

DEOGEN2

Benign

0.062

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.023

M_CAP

Benign

0.0028

MetaRNN

Benign

0.050

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

-0.60

PrimateAI

Benign

0.38

PROVEAN

Pathogenic

-7.7

REVEL

Benign

0.10

Sift

Benign

0.55

Sift4G

Benign

0.51

Polyphen

0.0

Vest4

0.14

MutPred

0.22

Loss of stability (P = 0.0038);

MVP

0.23

ClinPred

0.050

GERP RS

-3.0

Varity_R

0.27

gMVP

0.0065

Mutation Taster

=100/0

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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rs1478683393

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over