chr10-87862043-A-T
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 Benign (★★).
Frequency
Genomes: 𝑓 0.0050 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0044 ( 57 hom. )
Consequence
KLLN
NM_001126049.2 missense
NM_001126049.2 missense
Scores
4
1
12
Clinical Significance
Conservation
PhyloP100: 0.290
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]
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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 [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 GnomAd at 763 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KLLN | NM_001126049.2 | c.445T>A | p.Trp149Arg | missense_variant | 1/1 | ENST00000445946.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KLLN | ENST00000445946.5 | c.445T>A | p.Trp149Arg | missense_variant | 1/1 | NM_001126049.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00501 AC: 763AN: 152202Hom.: 5 Cov.: 32
GnomAD3 genomes
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GnomAD3 exomes AF: 0.00654 AC: 675AN: 103242Hom.: 5 AF XY: 0.00719 AC XY: 380AN XY: 52868
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GnomAD4 exome AF: 0.00440 AC: 5887AN: 1338266Hom.: 57 Cov.: 31 AF XY: 0.00478 AC XY: 3128AN XY: 654270
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GnomAD4 genome ? AF: 0.00504 AC: 767AN: 152320Hom.: 6 Cov.: 32 AF XY: 0.00499 AC XY: 372AN XY: 74488
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ESP6500AA
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8
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ExAC
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164
Asia WGS
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41
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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: BS1, BS2 - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationAssessor
Benign
N
MutationTaster
Benign
N
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D
REVEL
Benign
Sift
Pathogenic
D
Sift4G
Pathogenic
D
Polyphen
B
Vest4
MutPred
Gain of disorder (P = 0.0032);
MVP
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AG_spliceai
Position offset: -2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at