6-150065524-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_024518.3(ULBP3):​c.502C>T​(p.Arg168Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000341 in 1,613,952 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000036 ( 1 hom. )

Consequence

ULBP3
NM_024518.3 missense

Scores

1
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -4.23
Variant links:
Genes affected
ULBP3 (HGNC:14895): (UL16 binding protein 3) The protein encoded by this gene is one of several related ligands of the KLRK1/NKG2D receptor, which is found in primary NK cells. Binding of these ligands to the receptor activates several signal transduction pathways, including the JAK2, STAT5, and ERK pathways. The encoded protein is expressed solubly and on the surface of many tumor cells, making it potentially an important target for therapeutics. [provided by RefSeq, Nov 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

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=0.033017844).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ULBP3NM_024518.3 linkc.502C>T p.Arg168Trp missense_variant Exon 3 of 5 ENST00000367339.7 NP_078794.1 Q9BZM4

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ULBP3ENST00000367339.7 linkc.502C>T p.Arg168Trp missense_variant Exon 3 of 5 5 NM_024518.3 ENSP00000356308.1 Q9BZM4
ULBP3ENST00000438272.2 linkc.502C>T p.Arg168Trp missense_variant Exon 3 of 4 1 ENSP00000403562.2 Q9BZM4

Frequencies

GnomAD3 genomes
AF:
0.0000132
AC:
2
AN:
152060
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000477
AC:
12
AN:
251492
Hom.:
0
AF XY:
0.0000368
AC XY:
5
AN XY:
135920
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.0000578
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000163
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000439
Gnomad OTH exome
AF:
0.000163
GnomAD4 exome
AF:
0.0000363
AC:
53
AN:
1461892
Hom.:
1
Cov.:
33
AF XY:
0.0000330
AC XY:
24
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.0000671
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000297
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000132
AC:
2
AN:
152060
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74270
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000652
Hom.:
2
Bravo
AF:
0.0000189
ExAC
AF:
0.0000494
AC:
6
EpiCase
AF:
0.00
EpiControl
AF:
0.0000593

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Jul 05, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.502C>T (p.R168W) alteration is located in exon 3 (coding exon 3) of the ULBP3 gene. This alteration results from a C to T substitution at nucleotide position 502, causing the arginine (R) at amino acid position 168 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.13
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.69
CADD
Benign
0.024
DANN
Benign
0.82
DEOGEN2
Benign
0.0072
T;T
Eigen
Benign
-2.0
Eigen_PC
Benign
-2.1
FATHMM_MKL
Benign
0.0021
N
LIST_S2
Benign
0.21
.;T
M_CAP
Benign
0.0030
T
MetaRNN
Benign
0.033
T;T
MetaSVM
Benign
-0.93
T
PrimateAI
Benign
0.23
T
PROVEAN
Uncertain
-2.7
D;D
REVEL
Benign
0.044
Sift
Benign
0.14
T;T
Sift4G
Benign
0.093
T;T
Polyphen
0.051
B;B
Vest4
0.13
MutPred
0.44
Loss of disorder (P = 0.0264);Loss of disorder (P = 0.0264);
MVP
0.19
MPC
0.48
ClinPred
0.023
T
GERP RS
-6.7
Varity_R
0.089
gMVP
0.20

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: rs35696295; hg19: chr6-150386660; API