19-54819844-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_013289.4(KIR3DL1):ā€‹c.487G>Cā€‹(p.Asp163His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,460,508 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 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. D163N) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000027 ( 0 hom. )

Consequence

KIR3DL1
NM_013289.4 missense

Scores

1
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.39
Variant links:
Genes affected
KIR3DL1 (HGNC:6338): (killer cell immunoglobulin like receptor, three Ig domains and long cytoplasmic tail 1) Killer cell immunoglobulin-like receptors (KIRs) are transmembrane glycoproteins expressed by natural killer cells and subsets of T cells. The KIR genes are polymorphic and highly homologous and they are found in a cluster on chromosome 19q13.4 within the 1 Mb leukocyte receptor complex (LRC). The gene content of the KIR gene cluster varies among haplotypes, although several "framework" genes are found in all haplotypes (KIR3DL3, KIR3DP1, KIR3DL4, KIR3DL2). The KIR proteins are classified by the number of extracellular immunoglobulin domains (2D or 3D) and by whether they have a long (L) or short (S) cytoplasmic domain. KIR proteins with the long cytoplasmic domain transduce inhibitory signals upon ligand binding via an immune tyrosine-based inhibitory motif (ITIM), while KIR proteins with the short cytoplasmic domain lack the ITIM motif and instead associate with the TYRO protein tyrosine kinase binding protein to transduce activating signals. The ligands for several KIR proteins are subsets of HLA class I molecules; thus, KIR proteins are thought to play an important role in regulation of the immune response. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.13345492).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
KIR3DL1NM_013289.4 linkc.487G>C p.Asp163His missense_variant Exon 4 of 9 NP_037421.2 P43629-1Q5UCE2Q8N6C9

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
KIR3DL1ENST00000391728.8 linkc.487G>C p.Asp163His missense_variant Exon 4 of 9 1 ENSP00000375608.4 P43629-1
KIR3DL1ENST00000326542.11 linkc.487G>C p.Asp163His missense_variant Exon 4 of 8 1 ENSP00000326868.7 W5QJC1
KIR3DL1ENST00000358178.4 linkc.202G>C p.Asp68His missense_variant Exon 3 of 8 1 ENSP00000350901.4 P43629-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000274
AC:
4
AN:
1460508
Hom.:
0
Cov.:
34
AF XY:
0.00000275
AC XY:
2
AN XY:
726542
show subpopulations
Gnomad4 AFR exome
AF:
0.000120
Gnomad4 AMR exome
AF:
0.00
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:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.15
BayesDel_addAF
Benign
-0.30
T
BayesDel_noAF
Benign
-0.67
CADD
Benign
0.043
DANN
Benign
0.96
DEOGEN2
Benign
0.0028
T;.;.
Eigen
Benign
-0.86
Eigen_PC
Benign
-1.0
FATHMM_MKL
Benign
0.0060
N
M_CAP
Benign
0.0010
T
MetaRNN
Benign
0.13
T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.72
N;.;.
PROVEAN
Benign
-1.8
N;N;N
REVEL
Benign
0.012
Sift
Pathogenic
0.0
D;D;D
Sift4G
Benign
0.62
T;T;T
Polyphen
0.15
B;.;.
Vest4
0.11
MutPred
0.27
Loss of ubiquitination at K162 (P = 0.0464);Loss of ubiquitination at K162 (P = 0.0464);.;
MVP
0.099
MPC
0.53
ClinPred
0.22
T
GERP RS
0.29
Varity_R
0.36
gMVP
0.048

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs62124101; hg19: chr19-55331299; COSMIC: COSV58494785; API