10-87862193-A-AACC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 1P and 6B. PM4_Supporting BP6_Moderate BS2

The NM_001126049.2(KLLN):c.294_295insGGT(p.Trp98_Cys99insGly) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000876 in 1,551,650 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00053 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000040 (0 hom.)
• Consequence: KLLN NM_001126049.2 inframe_insertion
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.374

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• PM4: Nonframeshift variant in NON repetitive region in NM_001126049.2. Strenght limited to Supporting due to length of the change: 1aa.
• BP6: Variant 10-87862193-A-AACC is Benign according to our data. Variant chr10-87862193-A-AACC is described in ClinVar as [Likely_benign]. Clinvar id is 3046404.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomAd at 80 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KLLN	NM_001126049.2	c.294_295insGGT	p.Trp98_Cys99insGly	inframe_insertion	1/1	ENST00000445946.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLLN	ENST00000445946.5	c.294_295insGGT	p.Trp98_Cys99insGly	inframe_insertion	1/1		NM_001126049.2	P1

Frequencies

GnomAD3 genomes AF: 0.000526 AC: 80 AN: 152214 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00186

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000196

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000910 AC: 14 AN: 153892 Hom.: 0 AF XY: 0.0000734 AC XY: 6 AN XY: 81704

Gnomad AFR exome AF: 0.00152

Gnomad AMR exome AF: 0.0000810

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000400 AC: 56 AN: 1399318 Hom.: 0 Cov.: 31 AF XY: 0.0000377 AC XY: 26 AN XY: 690164

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.000112

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000690

GnomAD4 genome AF: 0.000525 AC: 80 AN: 152332 Hom.: 0 Cov.: 32 AF XY: 0.000550 AC XY: 41 AN XY: 74486

Gnomad4 AFR AF: 0.00185

Gnomad4 AMR AF: 0.000196

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

KLLN-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Apr 06, 2022

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs781685752; hg19: chr10-89621950;