rs1478683393

Variant names:

• chr10-87862046-A-C
• rs1478683393
• NM_001126049.2:c.442T>G

Your query was ambiguous. Multiple possible variants found:

• chr10-87862046-A-C
• chr10-87862046-A-G
• chr10-87862046-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_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. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.5e-7 (0 hom.)
• Consequence: KLLN NM_001126049.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.600

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 -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	c.442T>G	p.Cys148Gly	missense_variant	Exon 1 of 1	ENST00000445946.5	NP_001119521.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLLN	ENST00000445946.5	c.442T>G	p.Cys148Gly	missense_variant	Exon 1 of 1	6	NM_001126049.2	ENSP00000392204.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000971 AC: 1 AN: 102976 Hom.: 0 AF XY: 0.0000190 AC XY: 1 AN XY: 52666

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 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: 7.47e-7 AC: 1 AN: 1338130 Hom.: 0 Cov.: 31 AF XY: 0.00000153 AC XY: 1 AN XY: 654192

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000283

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

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	T
BayesDel_noAF	Benign	-0.36
CADD	Benign	8.9
DANN	Benign	0.64
DEOGEN2	Benign	0.062	T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.023	N
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.050	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PrimateAI	Benign	0.38	T
PROVEAN	Pathogenic	-7.7	D
REVEL	Benign	0.10
Sift	Benign	0.55	T
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.14
MutPred		0.22		Loss of stability (P = 0.0038);
MVP		0.23
ClinPred		0.050	T
GERP RS		-3.0
Varity_R		0.27
gMVP		0.0065

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

Other links and lift over

dbSNP: rs1478683393; hg19: chr10-89621803;